EVIDENCE FOR PREFERENTIAL ADHESION OF OVARIAN EPITHELIAL CARCINOMA-CELLS TO TYPE-I COLLAGEN MEDIATED BY THE ALPHA-2-BETA-1 INTEGRIN

Epithelial ovarian carcinoma, the leading cause of gynecologic cancer death, is characterized by widespread intra-abdominal metastases media ted primarily by surface shedding of tumor cells and peritoneal implan tation. Whereas hematogenous metastasis is known to involve cellular a dhesion, extracellular matrix proteolysis and cell migration, the role of these processes in the intraperitoneal dissemination of ovarian ca ncer remains unclear. To analyze further the role of adhesion and prot eolysis in ovarian carcinoma dissemination, we have characterized the adhesive profiles of 4 primary cultures of ovarian carcinoma cells and 5 ovarian carcinoma cell lines. Our data demonstrate preferential adh esion of ovarian carcinoma cells to interstitial type I collagen. Anal ysis of adhesion molecule expression demonstrated the presence of the alpha 2 and beta 1 integrin subunits by cell surface ELISA, immunoprec ipitation and immunohistochemistry. Furthermore, antibodies directed a gainst the alpha 2 and beta 1 subunits inhibited adhesion of ovarian c arcinoma cells to type I collagen by 56% and 95%, respectively. Plasmi nogen activator and matrix metalloproteinase production by adherent ce lls was not altered as a consequence of adhesion to individual extrace llular matrix proteins; however, adhesion to an extracellular matrix c omprised primarily of interstitial collagen increased plasminogen acti vator activity in 5 of 5 cell lines. Since the ovarian carcinoma micro -environment is rich in type collagen, our data suggest that preferent ial adhesion to type I collagen followed by secretion of serine and me talloproteinases may represent a biochemical mechanism by which the in traperitoneal dissemination of ovarian carcinoma is mediated. (C) 1996 Wiley-Liss, Inc.