PubMed:11235952
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/11235952","sourcedb":"PubMed","sourceid":"11235952","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/11235952","text":"Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma.\nOBJECT: Acquisition of invasive and metastatic potentials through proteinase expression is an essential event in tumor progression. Among proteinases, matrix metalloproteinases (MMPs) are thought to play a key role in tumor progression through the degradation of the extracellular matrix. In the present study, the authors examined the role of MMP-2 (gelatinase A) and membrane type 1 MMP (MT1-MMP), an activator of the zymogen of MMP-2, proMMP-2, together with tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in the invasion of astrocytic tumors in humans.\nMETHODS: Analyses performed using sandwich enzyme immunoassays demonstrated that the production levels of pro-MMP-2 and TIMP-1, but not TIMP-2, are significantly higher in glioblastomas multiforme than in other grades of astrocytic tumors. Quantitative reverse transcription-polymerase chain reaction indicated that MT1-MMP is expressed predominantly in glioblastoma tissues, and its expression levels are significantly enhanced as tumor grade increases. In addition, the expression levels and proMMP-2 activation ratio were remarkably higher in glioblastomas associated with cerebrospinal fluid (CSF) dissemination than in those not associated with CSF dissemination. In contrast, an examination of TIMP-2 levels showed a reverse correlation. Like MT1-MMP, TIMP-1 and TIMP-2 were immunolocalized to neoplastic cells in glioblastoma samples. To study the roles of these molecules in the invasion of astrocytic tumors more fully, stable transfectants expressing the MT1-MMP gene were developed in a U251 human glioblastoma cell line. The MT1-MMP transfectants displayed prominent activation of proMMP-2 and invasive growth in three-dimensional collagen gel; however, mock transfectants and parental cells displayed noninvasive growth without the activation. The invasion and gelatinolytic activity of the transfectants were completely inhibited by addition of recombinant TIMP-2, but not recombinant TIMP-1.\nCONCLUSIONS: These results indicate that MT1-MMP may contribute to tumor invasion and CSF dissemination of glioblastoma cells on the basis of an imbalance of TIMP-2.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":54,"end":94},"obj":"gene:7077"},{"id":"T1","span":{"begin":134,"end":150},"obj":"disease:C0555198"},{"id":"T2","span":{"begin":9,"end":49},"obj":"gene:4323"},{"id":"T3","span":{"begin":134,"end":150},"obj":"disease:C0555198"},{"id":"T4","span":{"begin":1038,"end":1045},"obj":"gene:4323"},{"id":"T5","span":{"begin":1076,"end":1088},"obj":"disease:C0017636"},{"id":"T6","span":{"begin":1491,"end":1497},"obj":"gene:7077"},{"id":"T7","span":{"begin":1542,"end":1554},"obj":"disease:C0017636"}],"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"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"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"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"11235952-0#9#49#gene4323","span":{"begin":9,"end":49},"obj":"gene4323"},{"id":"11235952-0#54#94#gene7077","span":{"begin":54,"end":94},"obj":"gene7077"},{"id":"11235952-0#134#150#diseaseC0555198","span":{"begin":134,"end":150},"obj":"diseaseC0555198"},{"id":"11235952-12#28#35#gene4323","span":{"begin":2170,"end":2177},"obj":"gene4323"},{"id":"11235952-12#145#151#gene7077","span":{"begin":2287,"end":2293},"obj":"gene7077"},{"id":"11235952-12#94#106#diseaseC0017636","span":{"begin":2236,"end":2248},"obj":"diseaseC0017636"},{"id":"11235952-4#111#117#gene7076","span":{"begin":842,"end":848},"obj":"gene7076"},{"id":"11235952-4#163#176#diseaseC0017636","span":{"begin":894,"end":907},"obj":"diseaseC0017636"}],"relations":[{"id":"9#49#gene4323134#150#diseaseC0555198","pred":"associated_with","subj":"11235952-0#9#49#gene4323","obj":"11235952-0#134#150#diseaseC0555198"},{"id":"54#94#gene7077134#150#diseaseC0555198","pred":"associated_with","subj":"11235952-0#54#94#gene7077","obj":"11235952-0#134#150#diseaseC0555198"},{"id":"28#35#gene432394#106#diseaseC0017636","pred":"associated_with","subj":"11235952-12#28#35#gene4323","obj":"11235952-12#94#106#diseaseC0017636"},{"id":"145#151#gene707794#106#diseaseC0017636","pred":"associated_with","subj":"11235952-12#145#151#gene7077","obj":"11235952-12#94#106#diseaseC0017636"},{"id":"111#117#gene7076163#176#diseaseC0017636","pred":"associated_with","subj":"11235952-4#111#117#gene7076","obj":"11235952-4#163#176#diseaseC0017636"}],"attributes":[{"subj":"11235952-0#9#49#gene4323","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-0#54#94#gene7077","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-0#134#150#diseaseC0555198","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-12#28#35#gene4323","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-12#145#151#gene7077","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-12#94#106#diseaseC0017636","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-4#111#117#gene7076","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11235952-4#163#176#diseaseC0017636","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":160,"end":721},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":731,"end":2128},"obj":"METHODS"},{"id":"T3","span":{"begin":2142,"end":2294},"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"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#d1ec93","default":true},{"id":"DisGeNET5_gene_disease","color":"#ec93eb"},{"id":"PubMed_Structured_Abstracts","color":"#93ecd3"}]}]}}