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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
We evaluated cellular mechanisms involved in the activation pathway of matrix prometalloproteinase-2 (pro-MMP-2), an enzyme implicated in the malignant progression of many tumor types. Membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves the N-terminal prodomain of pro-MMP-2 thus generating the activation intermediate that then matures into the fully active enzyme of MMP-2. Our results provide evidence on how a collaboration between MT1-MMP and integrin alphavbeta3 promotes more efficient activation and specific, transient docking of the activation intermediate and, further, the mature, active enzyme of MMP-2 at discrete regions of cells. We show that coexpression of MT1-MMP and integrin alphavbeta3 in MCF7 breast carcinoma cells specifically enhances in trans autocatalytic maturation of MMP-2. The association of MMP-2's C-terminal hemopexin-like domain with those molecules of integrin alphavbeta3 which are proximal to MT1-MMP facilitates MMP-2 maturation. Vitronectin, a specific ligand of integrin alphavbeta3, competitively blocked the integrin-dependent maturation of MMP-2. Immunofluorescence and immunoprecipitation studies supported clustering of MT1-MMP and integrin alphavbeta3 at discrete regions of the cell surface. Evidently, the identified mechanisms appear to be instrumental to clustering active MMP-2 directly at the invadopodia and invasive front of alphavbeta3-expressing cells or in their close vicinity, thereby accelerating tumor cell locomotion.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases...,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/PHEX Phosphate Regulating Neutral...,
http://linkedlifedata.com/resource/pubmed/chemical/PHEX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/Vitronectin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0014-4827
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
209-23
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11161720-Antibodies, Monoclonal,
pubmed-meshheading:11161720-Blotting, Western,
pubmed-meshheading:11161720-Breast Neoplasms,
pubmed-meshheading:11161720-Carcinoma,
pubmed-meshheading:11161720-Cell Movement,
pubmed-meshheading:11161720-Culture Media, Serum-Free,
pubmed-meshheading:11161720-Enzyme Activation,
pubmed-meshheading:11161720-Female,
pubmed-meshheading:11161720-Fibrosarcoma,
pubmed-meshheading:11161720-Flow Cytometry,
pubmed-meshheading:11161720-Glioma,
pubmed-meshheading:11161720-Humans,
pubmed-meshheading:11161720-Matrix Metalloproteinase 2,
pubmed-meshheading:11161720-Matrix Metalloproteinases, Membrane-Associated,
pubmed-meshheading:11161720-Metalloendopeptidases,
pubmed-meshheading:11161720-Microscopy, Confocal,
pubmed-meshheading:11161720-PHEX Phosphate Regulating Neutral Endopeptidase,
pubmed-meshheading:11161720-Protease Inhibitors,
pubmed-meshheading:11161720-Protein Precursors,
pubmed-meshheading:11161720-Proteins,
pubmed-meshheading:11161720-Receptors, Vitronectin,
pubmed-meshheading:11161720-Recombinant Fusion Proteins,
pubmed-meshheading:11161720-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:11161720-Transfection,
pubmed-meshheading:11161720-Tumor Cells, Cultured,
pubmed-meshheading:11161720-Vitronectin
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pubmed:year |
2001
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pubmed:articleTitle |
MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells.
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pubmed:affiliation |
The Burnham Institute, La Jolla, California, 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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