Membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation in primary human ovarian epithelial carcinoma cells

Metastatic dissemination of epithelial ovarian carcinoma occurs primarily through exfoliation of cells from the primary tumor, with subsequent implantation, invasion, and growth throughout the organs within the peritoneal cavity. Previous studies have suggested a role for matrix metalloproteinases (...

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Bibliographic Details
Published inInvasion and metastasis Vol. 16; no. 3; p. 150
Main Authors Fishman, D A, Bafetti, L M, Stack, M S
Format Journal Article
LanguageEnglish
Published Switzerland 1996
Subjects
Carcinoma - chemistry
Carcinoma - drug therapy
Carcinoma - enzymology
Collagen - metabolism
Concanavalin A - pharmacology
Culture Media, Conditioned
Drug Combinations
Female
Gelatinases - analysis
Gelatinases - biosynthesis
Humans
Immunohistochemistry
Laminin - metabolism
Matrix Metalloproteinase 2
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases - analysis
Metalloendopeptidases - biosynthesis
Neoplasm Invasiveness
Ovarian Neoplasms - chemistry
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - enzymology
Proteoglycans - metabolism
Tumor Cells, Cultured
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Summary:Metastatic dissemination of epithelial ovarian carcinoma occurs primarily through exfoliation of cells from the primary tumor, with subsequent implantation, invasion, and growth throughout the organs within the peritoneal cavity. Previous studies have suggested a role for matrix metalloproteinases (MMPs), particularly MMP-2, in ovarian cancer invasion and metastasis. To characterize further the role of MMPs and their inhibitors in ovarian carcinoma, in this study the production and activation of MMPs by short-term primary cultures of human ovarian epithelial carcinoma cells were analyzed. We report that MMP-2 is the predominant gelatinolytic MMP secreted by primary ovarian cancer cells derived from both ovarian tumors and ascites fluid. Furthermore, zymographic analysis demonstrated that MMP-2 is present in conditioned media in both the latent and activated forms, indicating that primary ovarian cancer cells catalyze proMMP-2 activation. Presence of a proMMP-2 activator was confirmed by immunohistochemistry and immunoprecipitation studies which found membrane-type 1 MMP (MT1-MMP) in the membranes of unstimulated cells and levels of both MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) were enhanced by culturing cells in the presence of concanavalin A. In addition, interaction of MMP-2 with the ovarian carcinoma cell surface resulted in a 2.5- to 5-fold increase in invasiveness. These data suggest that MT1-MMP-catalyzed activation of proMMP-2 may play a physiologic role in intraperitoneal invasion of ovarian carcinoma cells.
ISSN:0251-1789