title: Fibronectin secretion from human peritoneal tissue induces Mr 92,000 type IV collagenase expression and invasion in ovarian cancer cell lines.
abstract: Our previous study showed that human peritoneal conditioned medium (CM) increased the matrix metalloproteinase-9 (MMP-9) secretion and invasiveness of ovarian cancer cells (NOM1). In an effort to identify this MMP-9-stimulating factor, we examined the effects of extracellular matrix components, such as type IV collagen, laminin, and fibronectin, on ovarian cancer cells. We found that fibronectin increased the MMP-9 activity of NOM1 cell CM in a concentration-dependent manner and that the peritoneal CM contained high level of fibronectin. An increase of MMP-9 activity in NOM1 cell CM by the peritoneal CM was almost completely blocked by 20 microg/ml of anti-integrin alpha5/FnR antibody and RGD polypeptides. Furthermore, after immunoprecipitation by antifibronectin antibody supernatant of the peritoneal CM did not increase MMP-9 activity in NOM1 cells. Fibronectin and the peritoneal CM also increased MMP-9 activity and expression in NOM1 cell lysate, and these effects were blocked by anti-integrin alpha5/FnR antibody. Invasiveness of NOM1 cells was enhanced by fibronectin and the peritoneal CM in a concentration-dependent manner, and anti-integrin alpha5/FnR antibody blocked these effects. These results suggested that fibronectin secreted from peritoneum increased MMP-9 activity and expression, and, in turn, invasiveness of ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.forename: F
authors.initials: F
authors.lastname: Kikkawa
authors.forename: A
authors.initials: A
authors.lastname: Nawa
authors.forename: N
authors.initials: N
authors.lastname: Suganuma
authors.forename: M
authors.initials: M
authors.lastname: Hamaguchi
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D017364:Collagenases / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D003536:Cystadenocarcinoma / Q000201:enzymology / Q000473:pathology; D004790:Enzyme Induction; D005260:Female; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D039482:Integrin alpha5; D007700:Kinetics; D020780:Matrix Metalloproteinase 9; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010537:Peritoneum / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D017469:Receptors, Fibronectin / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017077:Culture Media, Conditioned; D005353:Fibronectins; D039482:Integrin alpha5; D017469:Receptors, Fibronectin; D017364:Collagenases; D020780:Matrix Metalloproteinase 9