PubMed:12548614 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/12548614","sourcedb":"PubMed","sourceid":"12548614","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/12548614","text":"Protease-activated receptor (PAR)-1 and PAR-2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomas.\nBACKGROUND: Cell growth can be induced via elicitation of protease-activated receptors (PAR) with serine proteases such as thrombin and trypsin.\nMETHODS: To understand whether PAR are involved in tumor vessel formation in the neoplastic cell-bearing alveolar walls, immunohistochemical and reverse transcriptase-polymerase chain reaction analyses were performed using the lung tissues from 16 patients with primary lung adenocarcinomas.\nRESULTS: In microdissected tumor alveolar walls, the expressions of PAR-1 and PAR-2 mRNA were increased by 10-fold (P \u003c 0.05) and 16-fold (P \u003c 0.01), respectively, as compared with normal alveolar walls. Confocal microscopy revealed that tumor capillary endothelial cells in alveolar walls lost thrombomodulin expression. Instead, the expression of PAR-2 often became obvious at the normal border. Both PAR-1 and PAR-2 were expressed in the microvessel endothelial cells in tumors. Trypsin mRNA was expressed in 7 of the 16 cancer cell-bearing tissue specimens in contrast to 1 of the 14 normal alveolar walls. Immunohistochemically, trypsin was positive in the neoplastic cells from 10 patients and in lung adenocarcinoma cell lines (A549, HLC-1, LC-2, and PC-14). An in vitro assay showed a significant increase in idoxuridine (IdU) or bromodeoxyuridine uptake in human pulmonary artery endothelial cells and human umbilical cord vein endothelial cells after treatments with alpha-thrombin or activating peptides; SFLLRN for PAR-1 and SLIGKV for PAR-2, respectively.\nCONCLUSIONS: Thus, proliferation of alveolar capillary endothelial cells is initialized in part by PAR activation with serum thrombin and neoplastic cell-released trypsin. These results suggest a synergistic effect of PAR with vascular endothelial growth factor in alveolar angiogenesis.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":40,"end":45},"obj":"gene:55065"},{"id":"T1","span":{"begin":127,"end":142},"obj":"disease:C0001418"},{"id":"T2","span":{"begin":40,"end":45},"obj":"gene:2150"},{"id":"T3","span":{"begin":127,"end":142},"obj":"disease:C0001418"},{"id":"T4","span":{"begin":40,"end":45},"obj":"gene:8856"},{"id":"T5","span":{"begin":127,"end":142},"obj":"disease:C0001418"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"12548614-0#40#45#gene2150","span":{"begin":40,"end":45},"obj":"gene2150"},{"id":"12548614-0#40#45#gene8856","span":{"begin":40,"end":45},"obj":"gene8856"},{"id":"12548614-0#40#45#gene55065","span":{"begin":40,"end":45},"obj":"gene55065"},{"id":"12548614-0#127#142#diseaseC0001418","span":{"begin":127,"end":142},"obj":"diseaseC0001418"}],"relations":[{"id":"40#45#gene2150127#142#diseaseC0001418","pred":"associated_with","subj":"12548614-0#40#45#gene2150","obj":"12548614-0#127#142#diseaseC0001418"},{"id":"40#45#gene8856127#142#diseaseC0001418","pred":"associated_with","subj":"12548614-0#40#45#gene8856","obj":"12548614-0#127#142#diseaseC0001418"},{"id":"40#45#gene55065127#142#diseaseC0001418","pred":"associated_with","subj":"12548614-0#40#45#gene55065","obj":"12548614-0#127#142#diseaseC0001418"}],"attributes":[{"subj":"12548614-0#40#45#gene2150","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12548614-0#40#45#gene8856","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12548614-0#40#45#gene55065","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12548614-0#127#142#diseaseC0001418","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":156,"end":288},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":298,"end":580},"obj":"METHODS"},{"id":"T3","span":{"begin":590,"end":1649},"obj":"RESULTS"},{"id":"T4","span":{"begin":1663,"end":1937},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#ec93e4","default":true},{"id":"DisGeNET5_gene_disease","color":"#93ecda"},{"id":"PubMed_Structured_Abstracts","color":"#ecc093"}]}]}}