Open AccessCoordinate action of membrane‐type matrix metalloproteinase‐1 (MT1‐MMP) and MMP‐2 enhances pericellular proteolysis and invasion
Author(s) -
Sato Hiroshi,
Takino Takahisa
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01498.x
Subject(s) - matrix metalloproteinase , proteolysis , microbiology and biotechnology , metalloproteinase , chemistry , gelatinase , extracellular matrix , gelatinase a , compartmentalization (fire protection) , tissue inhibitor of metalloproteinase , biochemistry , biology , enzyme
Membrane‐type matrix metalloproteinase‐1 (MT1‐MMP) mediates cleavage of not only MMP‐2/gelatinase A for activation, but also a variety of substrates including type I collagen (reviewed in Cancer Sci 2005; 96: 212–7). MMP‐2 activation involves tissue inhibitor of MMP (TIMP)‐2 as a bridging molecule between MT1‐MMP and pro‐MMP‐2. Thus, net activity of MT1‐MMP and MMP‐2 is regulated in a complex manner depending on TIMP‐2 concentration. During invasive growth of tumor cells in type I collagen matrix, MT1‐MMP initiates denaturation of collagen into gelatin, which is subsequently digested further by MMP‐2 adjacent to MT1‐MMP. Coordinate action of MT1‐MMP and MMP‐2 may facilitate pericellular proteolysis, and enhance not only tumor invasion/migration but also cell growth. Tetraspanins as binding proteins of MT1‐MMP regulate MT1‐MMP subcellular localization and compartmentalization, leading to efficient MMP‐2 activation and proteolysis coupled with cellular function. ( Cancer Sci 2010; 101: 843–847)