EXPRESSION AND FUNCTION OF BETA-1 AND ALPHA-V-BETA-3 INTEGRINS IN OVARIAN-CANCER

Ovarian cancer cells disseminate by implanting onto the peritoneal mes othelial cell surface of the abdominal cavity. A common feature of the se peritoneal implants is the presence of tumor cell. invasion into th e submesothelial extracellular matrix (ECM). In view of the important role of integrins in ECM recognition and cell migration, we were inter ested in defining the pattern of integrin expression and function in o varian cancer cell lines and primary tissue samples. The beta 1 integr in chain was expressed by CAOV-3, SKOV-3, OVCAR-3, and SW626 ovarian c ancer cell lines, associated with expression of alpha 1, -2, -3, -5, a nd -6 chains. The alpha 4 chain was also expressed by two of the four Lines. In addition to beta 1 integrins, the alpha v beta 3 integrin wa s also expressed, although there was no expression of beta 2, -4, and -7 chains. Immunoprecipitation of surface-labeled CAOV-3 cells with an anti-beta 1 antibody revealed a band at approximate to 110-130 kDa co nsistent with the known molecular mass of the beta 1 chain, as well as several associated bands consistent with noncovalently linked integri n cr chains. A similar pattern of beta 1 and alpha v beta 3 integrin e xpression was observed for primary ovarian cancer tissue samples. Ovar ian cancer cell lines exhibited significant binding to collagen type I and laminin which was primarily mediated by beta 1 integrins. In cont rast, ovarian cancer cell binding to fibronectin was mediated by both alpha 5 beta 1 and alpha v beta 3 integrins. Even though mesothelial c ells were observed to express fibronectin mRNA and protein, binding of ovarian cancer cells to peritoneal mesothelium was not blocked by neu tralizing antibodies to beta 1 or alpha v beta 3 integrins. These data suggest that functional integrins are commonly expressed by ovarian c ancer cells, although they do not appear to mediate ovarian cancer cel l implantation onto peritoneal mesothelium. The role that integrins pl ay in the invasion of ovarian cancer cells into the submesothelial ECM deserves further investigation. (C) 1995 Academic Press, Inc.