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Matrilysin (MMP‐7) promotes invasion of ovarian cancer cells by activation of progelatinase
Author(s) -
Wang Fengqiang,
So John,
Reierstad Scott,
Fishman David A.
Publication year - 2005
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/ijc.20697
Subject(s) - matrilysin , matrix metalloproteinase , mmp2 , ovarian cancer , metastasis , cancer research , in vitro , in vivo , gelatinase a , ovarian carcinoma , metalloproteinase , cell culture , cell , biology , gelatinase , chemistry , cancer , medicine , biochemistry , genetics , microbiology and biotechnology
Although matrilysin (MMP‐7) is overexpressed in various malignancies, few studies have evaluated its role in epithelial ovarian cancer (EOC) invasion and metastasis. We report that the secretion of MMP‐7 in EOC is stimulated significantly by vascular endothelial growth factor (VEGF) and interlukin‐8 (IL‐8). We also examined the in vivo expression of MMP‐7 in EOC and its effects on the in vitro invasion and progelatinase activation. We report that MMP‐7 is overexpressed in ovarian cancer cell lines and EOC surgical specimens. DOV13 cells incubated with active rhMMP‐7 significantly increased cellular invasion and proMMP‐2 activation. RhMMP‐7 also showed the ability to activate proMMP‐2 and proMMP‐9 in immortalized ovarian epithelial cell (IOSE‐29) conditioned medium. In addition, rhMMP‐7 was able to activate progelatinase in a concentration‐dependent manner in vitro . TIMP‐2 or the generic MMP inhibitor‐GM6001 inhibited both the activation of proMMP‐2 and the increased invasion of DOV13 cells promoted by rhMMP‐7. By incubation of MMP2‐TIMP‐2 complex with equal molar rhMMP‐7, MMP‐2 was dissociated from the complex and activated in a time‐dependent manner, suggesting that TIMP‐2 helps to keep the latency of MMP‐2. TIMP–2 also showed inhibitory effects on the MMP‐7 induced increase of gelatinolytic activity in DOV13 and IOSE‐29 conditioned media. A strong co‐localization of MMP‐7 and MMP‐2 was observed in DOV13 cells and ovarian carcinoma permanent tissue sections. These results indicate MMP‐7 is overexpressed in malignant ovarian epithelium and suggest MMP‐7 may facilitate tumor cell invasion in vivo partly through the induction of progelatinase activation. © 2004 Wiley‐Liss, Inc.