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Functional activation of integrin αvβ3 in tumor cells expressing membrane‐type 1 matrix metalloproteinase
Author(s) -
Deryugina Elena I.,
Bourdon Mario A.,
Jungwirth Karli,
Smith Jeffrey W.,
Strongin Alex Y.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000401)86:1<15::aid-ijc3>3.0.co;2-b
Subject(s) - matrix metalloproteinase , integrin , metalloproteinase , extracellular matrix , microbiology and biotechnology , matrix (chemical analysis) , cancer research , collagen receptor , chemistry , biology , medicine , cell , biochemistry , chromatography
Matrix metalloproteinases (MMPs) and integrins have been implicated in a variety of processes involved in tumor progression. To evaluate the individual roles of integrin αvβ3 and membrane‐type 1 matrix metalloproteinase (MT1‐MMP), as well as the effects of their joint expression on tumor cell functions, MCF7 breast carcinoma cells were transfected stably with either the MT1‐MMP, the β3 integrin subunit or both MT1‐MMP and β3 cDNAs. MT1‐MMP expression is accompanied by the functional activation of integrin αvβ3, thereby increasing vitronectin‐mediated adhesion and migration of MCF7 cells transfected with MT1‐MMP and integrin αvβ3. MT1‐MMP‐dependent functional activation of αvβ3 correlates with modification(s) of the β3 subunit, including its higher electrophoretic mobility and affected the LM609‐binding site. MCF7 cells jointly expressing MT1‐MMP and αvβ3 were the most efficient in adhesion to the recombinant C‐terminal domain of MMP‐2 as well as in generating soluble and cell surface associated mature MMP‐2 enzyme. These findings suggest a mechanism of selective docking of MMP‐2 at tumor cell surfaces, specifically at the sites that include MT1‐MMP and activated integrin αvβ3. These mechanisms may provide a link between spatial regulation of focal proteolysis by the cell surface associated MMPs and the regulation of integrin‐mediated motility of tumor cells. Int. J. Cancer 86:15–23, 2000. © 2000 Wiley‐Liss, Inc.