PubMed:23035012 JSON TXT

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CL-cell

Glycan-Motif

{"project":"Glycan-Motif","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"https://glytoucan.org/Structures/Glycans/G08371CD"},{"id":"T2","span":{"begin":55,"end":72},"obj":"https://glytoucan.org/Structures/Glycans/G36123IU"},{"id":"T3","span":{"begin":351,"end":361},"obj":"https://glytoucan.org/Structures/Glycans/G58507AZ"},{"id":"T4","span":{"begin":1311,"end":1323},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos6-Glycan-Motif-Image

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"Glycan_Motif"},{"id":"T3","span":{"begin":62,"end":72},"obj":"Glycan_Motif"},{"id":"T4","span":{"begin":351,"end":361},"obj":"Glycan_Motif"},{"id":"T5","span":{"begin":1311,"end":1323},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G36123IU"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G08371CD"},{"id":"A3","pred":"image","subj":"T3","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G57321FI"},{"id":"A4","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G58507AZ"},{"id":"A5","pred":"image","subj":"T5","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G81533KY"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Glycosmos6-MAT

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":976,"end":980},"obj":"http://purl.obolibrary.org/obo/MAT_0000135"},{"id":"T2","span":{"begin":1500,"end":1506},"obj":"http://purl.obolibrary.org/obo/MAT_0000085"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

sentences

GlyCosmos6-Glycan-Motif-Structure

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"https://glytoucan.org/Structures/Glycans/G08371CD"},{"id":"T2","span":{"begin":55,"end":72},"obj":"https://glytoucan.org/Structures/Glycans/G36123IU"},{"id":"T3","span":{"begin":62,"end":72},"obj":"https://glytoucan.org/Structures/Glycans/G57321FI"},{"id":"T4","span":{"begin":351,"end":361},"obj":"https://glytoucan.org/Structures/Glycans/G58507AZ"},{"id":"T5","span":{"begin":1311,"end":1323},"obj":"https://glytoucan.org/Structures/Glycans/G81533KY"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Glycosmos6-GlycoEpitope

{"project":"Glycosmos6-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"http://www.glycoepitope.jp/epitopes/EP0022"},{"id":"T2","span":{"begin":62,"end":72},"obj":"http://www.glycoepitope.jp/epitopes/EP0021"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlycoBiology-FMA

uniprot-human

uniprot-mouse

{"project":"uniprot-mouse","denotations":[{"id":"T1","span":{"begin":717,"end":742},"obj":"http://www.uniprot.org/uniprot/P01587"},{"id":"T2","span":{"begin":921,"end":924},"obj":"http://www.uniprot.org/uniprot/Q91X17"},{"id":"T3","span":{"begin":1144,"end":1147},"obj":"http://www.uniprot.org/uniprot/Q91X17"},{"id":"T4","span":{"begin":1618,"end":1621},"obj":"http://www.uniprot.org/uniprot/Q91X17"},{"id":"T5","span":{"begin":1500,"end":1522},"obj":"http://www.uniprot.org/uniprot/P48025"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlycoBiology-NCBITAXON

{"project":"GlycoBiology-NCBITAXON","denotations":[{"id":"T1","span":{"begin":525,"end":531},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/6754"},{"id":"T2","span":{"begin":532,"end":537},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T3","span":{"begin":624,"end":631},"obj":"http://purl.bioontology.org/ontology/STY/T024"},{"id":"T4","span":{"begin":857,"end":862},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T5","span":{"begin":880,"end":885},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T6","span":{"begin":901,"end":903},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/13893"},{"id":"T7","span":{"begin":954,"end":959},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T8","span":{"begin":981,"end":990},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/166034"},{"id":"T9","span":{"begin":992,"end":997},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T10","span":{"begin":1058,"end":1064},"obj":"http://purl.bioontology.org/ontology/NCBITAXON/6754"},{"id":"T11","span":{"begin":1065,"end":1070},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T12","span":{"begin":1150,"end":1155},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T13","span":{"begin":1209,"end":1214},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T14","span":{"begin":1624,"end":1629},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T15","span":{"begin":1758,"end":1766},"obj":"http://purl.bioontology.org/ontology/STY/T033"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GO-BP

{"project":"GO-BP","denotations":[{"id":"T1","span":{"begin":55,"end":61},"obj":"http://purl.obolibrary.org/obo/GO_0097503"},{"id":"T2","span":{"begin":335,"end":341},"obj":"http://purl.obolibrary.org/obo/GO_0097503"},{"id":"T3","span":{"begin":88,"end":97},"obj":"http://purl.obolibrary.org/obo/GO_0046903"},{"id":"T4","span":{"begin":1549,"end":1558},"obj":"http://purl.obolibrary.org/obo/GO_0046903"},{"id":"T5","span":{"begin":1869,"end":1878},"obj":"http://purl.obolibrary.org/obo/GO_0046903"},{"id":"T6","span":{"begin":805,"end":811},"obj":"http://purl.obolibrary.org/obo/GO_0040007"},{"id":"T7","span":{"begin":1163,"end":1171},"obj":"http://purl.obolibrary.org/obo/GO_0007349"},{"id":"T8","span":{"begin":1436,"end":1439},"obj":"http://purl.obolibrary.org/obo/GO_0050065"},{"id":"T9","span":{"begin":1666,"end":1669},"obj":"http://purl.obolibrary.org/obo/GO_0050065"},{"id":"T10","span":{"begin":1490,"end":1496},"obj":"http://purl.obolibrary.org/obo/GO_0023052"},{"id":"T11","span":{"begin":1843,"end":1849},"obj":"http://purl.obolibrary.org/obo/GO_0023052"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GO-MF

{"project":"GO-MF","denotations":[{"id":"T1","span":{"begin":1416,"end":1423},"obj":"http://purl.obolibrary.org/obo/GO_0070026"},{"id":"T2","span":{"begin":1416,"end":1423},"obj":"http://purl.obolibrary.org/obo/GO_0003680"},{"id":"T3","span":{"begin":1416,"end":1423},"obj":"http://purl.obolibrary.org/obo/GO_0017091"},{"id":"T4","span":{"begin":1416,"end":1423},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GO-CC

{"project":"GO-CC","denotations":[{"id":"T1","span":{"begin":532,"end":537},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T2","span":{"begin":857,"end":862},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T3","span":{"begin":880,"end":885},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T4","span":{"begin":954,"end":959},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T5","span":{"begin":992,"end":997},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T6","span":{"begin":1065,"end":1070},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T7","span":{"begin":1150,"end":1155},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T8","span":{"begin":1209,"end":1214},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T9","span":{"begin":1292,"end":1296},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T10","span":{"begin":1452,"end":1465},"obj":"http://purl.obolibrary.org/obo/GO_0016021"},{"id":"T11","span":{"begin":1452,"end":1465},"obj":"http://purl.obolibrary.org/obo/GO_0044214"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

UBERON-AE

{"project":"UBERON-AE","denotations":[{"id":"T1","span":{"begin":624,"end":631},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"T2","span":{"begin":976,"end":980},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"T3","span":{"begin":1500,"end":1506},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_23035012_1_0","span":{"begin":335,"end":344},"obj":"expanded"},{"id":"SS2_23035012_1_0","span":{"begin":346,"end":349},"obj":"abbr"},{"id":"SS1_23035012_3_0","span":{"begin":565,"end":593},"obj":"expanded"},{"id":"SS2_23035012_3_0","span":{"begin":595,"end":599},"obj":"abbr"},{"id":"SS1_23035012_4_0","span":{"begin":792,"end":820},"obj":"expanded"},{"id":"SS2_23035012_4_0","span":{"begin":822,"end":827},"obj":"abbr"},{"id":"SS1_23035012_7_0","span":{"begin":1367,"end":1400},"obj":"expanded"},{"id":"SS2_23035012_7_0","span":{"begin":1402,"end":1407},"obj":"abbr"},{"id":"SS1_23035012_7_1","span":{"begin":1500,"end":1522},"obj":"expanded"},{"id":"SS2_23035012_7_1","span":{"begin":1524,"end":1527},"obj":"abbr"}],"relations":[{"id":"AE1_23035012_1_0","pred":"abbreviatedTo","subj":"SS1_23035012_1_0","obj":"SS2_23035012_1_0"},{"id":"AE1_23035012_3_0","pred":"abbreviatedTo","subj":"SS1_23035012_3_0","obj":"SS2_23035012_3_0"},{"id":"AE1_23035012_4_0","pred":"abbreviatedTo","subj":"SS1_23035012_4_0","obj":"SS2_23035012_4_0"},{"id":"AE1_23035012_7_0","pred":"abbreviatedTo","subj":"SS1_23035012_7_0","obj":"SS2_23035012_7_0"},{"id":"AE1_23035012_7_1","pred":"abbreviatedTo","subj":"SS1_23035012_7_1","obj":"SS2_23035012_7_1"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":362,"end":367},"obj":"HP_0002664"},{"id":"T2","span":{"begin":525,"end":531},"obj":"HP_0002664"},{"id":"T3","span":{"begin":565,"end":570},"obj":"HP_0002664"},{"id":"T4","span":{"begin":618,"end":623},"obj":"HP_0002664"},{"id":"T5","span":{"begin":944,"end":952},"obj":"HP_0001909"},{"id":"T6","span":{"begin":1058,"end":1064},"obj":"HP_0002664"},{"id":"T7","span":{"begin":1806,"end":1813},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1955,"end":1960},"obj":"HP_0002664"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlycoBiology-MAT

{"project":"GlycoBiology-MAT","denotations":[{"id":"T1","span":{"begin":976,"end":980},"obj":"http://purl.obolibrary.org/obo/MAT_0000135"},{"id":"T2","span":{"begin":1500,"end":1506},"obj":"http://purl.obolibrary.org/obo/MAT_0000085"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Lectin

{"project":"Lectin","denotations":[{"id":"Lectin_T1","span":{"begin":62,"end":64},"obj":"https://acgg.asia/db/lfdb/LfDB0021"},{"id":"Lectin_T2","span":{"begin":342,"end":344},"obj":"https://acgg.asia/db/lfdb/LfDB0021"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlycoBiology-Epitope

{"project":"GlycoBiology-Epitope","denotations":[{"id":"PD-GlycoEpitope-B_T1","span":{"begin":62,"end":72},"obj":"http://www.glycoepitope.jp/epitopes/EP0021"},{"id":"PD-GlycoEpitope-B_T2","span":{"begin":55,"end":72},"obj":"http://www.glycoepitope.jp/epitopes/EP0022"},{"id":"PD-GlycoEpitope-B_T3","span":{"begin":751,"end":753},"obj":"http://www.glycoepitope.jp/epitopes/AN0542"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

performance-test

{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":624,"end":631},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":976,"end":980},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"PD-UBERON-AE-B_T3","span":{"begin":1500,"end":1506},"obj":"http://purl.obolibrary.org/obo/UBERON_0002106"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

mondo_disease

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":38,"end":43},"obj":"Disease"},{"id":"T2","span":{"begin":362,"end":367},"obj":"Disease"},{"id":"T3","span":{"begin":525,"end":531},"obj":"Disease"},{"id":"T4","span":{"begin":565,"end":570},"obj":"Disease"},{"id":"T5","span":{"begin":618,"end":623},"obj":"Disease"},{"id":"T6","span":{"begin":934,"end":952},"obj":"Disease"},{"id":"T8","span":{"begin":976,"end":990},"obj":"Disease"},{"id":"T9","span":{"begin":1058,"end":1064},"obj":"Disease"},{"id":"T10","span":{"begin":1955,"end":1960},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0004992"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0004600"},{"id":"A7","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0007896"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0005138"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/MONDO_0004992"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Anatomy-MAT

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":976,"end":980},"obj":"Body_part"},{"id":"T2","span":{"begin":1500,"end":1506},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000135"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000085"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Glycan-GlyCosmos

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":62,"end":72},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G57321FI"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G57321FI"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos-GlycoEpitope

{"project":"GlyCosmos-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0022"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-HP

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":38,"end":43},"obj":"Phenotype"},{"id":"T2","span":{"begin":362,"end":367},"obj":"Phenotype"},{"id":"T3","span":{"begin":525,"end":531},"obj":"Phenotype"},{"id":"T4","span":{"begin":565,"end":570},"obj":"Phenotype"},{"id":"T5","span":{"begin":618,"end":623},"obj":"Phenotype"},{"id":"T6","span":{"begin":944,"end":952},"obj":"Phenotype"},{"id":"T7","span":{"begin":981,"end":990},"obj":"Phenotype"},{"id":"T8","span":{"begin":1058,"end":1064},"obj":"Phenotype"},{"id":"T9","span":{"begin":1955,"end":1960},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002664"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0002664"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002664"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0002664"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"HP:0001909"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"HP:0030731"},{"id":"A8","pred":"hp_id","subj":"T8","obj":"HP:0002664"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"HP:0002664"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-CL

GlyCosmos15-UBERON

sentences

GlyCosmos15-Sentences

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":155},"obj":"Sentence"},{"id":"T2","span":{"begin":156,"end":396},"obj":"Sentence"},{"id":"T3","span":{"begin":397,"end":538},"obj":"Sentence"},{"id":"T4","span":{"begin":539,"end":632},"obj":"Sentence"},{"id":"T5","span":{"begin":633,"end":886},"obj":"Sentence"},{"id":"T6","span":{"begin":887,"end":1215},"obj":"Sentence"},{"id":"T7","span":{"begin":1216,"end":1324},"obj":"Sentence"},{"id":"T8","span":{"begin":1325,"end":1529},"obj":"Sentence"},{"id":"T9","span":{"begin":1530,"end":1751},"obj":"Sentence"},{"id":"T10","span":{"begin":1752,"end":2040},"obj":"Sentence"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-GlycoEpitope

{"project":"GlyCosmos15-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0022"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-Glycan

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":55,"end":72},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G36123IU"},{"id":"A2","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G36123IU"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-MONDO

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":38,"end":43},"obj":"Disease"},{"id":"T2","span":{"begin":362,"end":367},"obj":"Disease"},{"id":"T3","span":{"begin":525,"end":531},"obj":"Disease"},{"id":"T4","span":{"begin":565,"end":570},"obj":"Disease"},{"id":"T5","span":{"begin":618,"end":623},"obj":"Disease"},{"id":"T6","span":{"begin":934,"end":952},"obj":"Disease"},{"id":"T8","span":{"begin":976,"end":990},"obj":"Disease"},{"id":"T9","span":{"begin":1058,"end":1064},"obj":"Disease"},{"id":"T10","span":{"begin":1955,"end":1960},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0005070"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"MONDO:0005070"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"MONDO:0004992"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"MONDO:0005070"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"MONDO:0005070"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"MONDO:0004600"},{"id":"A7","pred":"mondo_id","subj":"T6","obj":"MONDO:0007896"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"MONDO:0005138"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"MONDO:0004992"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"MONDO:0005070"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-NCBITAXON

{"project":"GlyCosmos15-NCBITAXON","denotations":[{"id":"T1","span":{"begin":612,"end":617},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":928,"end":933},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":970,"end":975},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"}],"namespaces":[{"prefix":"_base","uri":"https://glycosmos.org/organisms/"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-FMA

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":103,"end":112},"obj":"Body_part"},{"id":"T2","span":{"begin":113,"end":124},"obj":"Body_part"},{"id":"T3","span":{"begin":289,"end":300},"obj":"Body_part"},{"id":"T4","span":{"begin":499,"end":508},"obj":"Body_part"},{"id":"T5","span":{"begin":509,"end":520},"obj":"Body_part"},{"id":"T6","span":{"begin":582,"end":593},"obj":"Body_part"},{"id":"T7","span":{"begin":624,"end":631},"obj":"Body_part"},{"id":"T8","span":{"begin":706,"end":716},"obj":"Body_part"},{"id":"T9","span":{"begin":759,"end":770},"obj":"Body_part"},{"id":"T10","span":{"begin":934,"end":943},"obj":"Body_part"},{"id":"T11","span":{"begin":976,"end":980},"obj":"Body_part"},{"id":"T12","span":{"begin":1032,"end":1041},"obj":"Body_part"},{"id":"T13","span":{"begin":1042,"end":1053},"obj":"Body_part"},{"id":"T14","span":{"begin":1500,"end":1506},"obj":"Body_part"},{"id":"T15","span":{"begin":1925,"end":1936},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:62864"},{"id":"A2","pred":"db_id","subj":"T2","obj":"FMA:63261"},{"id":"A3","pred":"db_id","subj":"T3","obj":"FMA:63261"},{"id":"A4","pred":"db_id","subj":"T4","obj":"FMA:62864"},{"id":"A5","pred":"db_id","subj":"T5","obj":"FMA:63261"},{"id":"A6","pred":"db_id","subj":"T6","obj":"FMA:63261"},{"id":"A7","pred":"db_id","subj":"T7","obj":"FMA:9637"},{"id":"A8","pred":"db_id","subj":"T8","obj":"FMA:63261"},{"id":"A9","pred":"db_id","subj":"T9","obj":"FMA:63261"},{"id":"A10","pred":"db_id","subj":"T10","obj":"FMA:62864"},{"id":"A11","pred":"db_id","subj":"T11","obj":"FMA:7195"},{"id":"A12","pred":"db_id","subj":"T12","obj":"FMA:62864"},{"id":"A13","pred":"db_id","subj":"T13","obj":"FMA:63261"},{"id":"A14","pred":"db_id","subj":"T14","obj":"FMA:7196"},{"id":"A15","pred":"db_id","subj":"T15","obj":"FMA:63261"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

GlyCosmos15-MAT

{"project":"GlyCosmos15-MAT","denotations":[{"id":"T1","span":{"begin":976,"end":980},"obj":"Body_part"},{"id":"T2","span":{"begin":1500,"end":1506},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000135"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000085"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

NCBITAXON

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":612,"end":617},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":928,"end":933},"obj":"OrganismTaxon"},{"id":"T3","span":{"begin":970,"end":975},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"9606"},{"id":"A3","pred":"db_id","subj":"T3","obj":"9606"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}

Anatomy-UBERON

HP-phenotype

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":38,"end":43},"obj":"Phenotype"},{"id":"T2","span":{"begin":362,"end":367},"obj":"Phenotype"},{"id":"T3","span":{"begin":525,"end":531},"obj":"Phenotype"},{"id":"T4","span":{"begin":565,"end":570},"obj":"Phenotype"},{"id":"T5","span":{"begin":618,"end":623},"obj":"Phenotype"},{"id":"T6","span":{"begin":944,"end":952},"obj":"Phenotype"},{"id":"T7","span":{"begin":981,"end":990},"obj":"Phenotype"},{"id":"T8","span":{"begin":1058,"end":1064},"obj":"Phenotype"},{"id":"T9","span":{"begin":1955,"end":1960},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002664"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0002664"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0002664"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0002664"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0002664"},{"id":"A6","pred":"hp_id","subj":"T6","obj":"HP:0001909"},{"id":"A7","pred":"hp_id","subj":"T7","obj":"HP:0030731"},{"id":"A8","pred":"hp_id","subj":"T8","obj":"HP:0002664"},{"id":"A9","pred":"hp_id","subj":"T9","obj":"HP:0002664"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.\nWe previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments."}