Expression and Function of β1 and αvβ3 Integrins in Ovarian Cancer

Abstract

Ovarian cancer cells disseminate by implanting onto the peritoneal mesothelial cell surface of the abdominal cavity. A common feature of these peritoneal implants is the presence of tumor cell invasion into the submesothelial extracellular matrix (ECM). In view of the important role of integrins in ECM recognition and cell migration, we were interested in defining the pattern of integrin expression and function in ovarian cancer cell lines and primary tissue samples. The β1 integrin chain was expressed by CAOV-3, SKOV-3, OVCAR-3, and SW626 ovarian cancer cell lines, associated with expression of α1, -2, -3, -5, and -6 chains. The α4 chain was also expressed by two of the four lines. In addition to β1 integrins, the αvβ3 integrin was also expressed, although there was no expression of β2, -4, and -7 chains. Immunoprecipitation of surface-labeled CAOV-3 cells with an anti-β2 antibody revealed a band at ≈110-130 kDa consistent with the known molecular mass of the β1 chain, as well as several associated bands consistent with noncovalently linked integrin α chains. A similar pattern of β1 and αvβ3 integrin expression was observed for primary ovarian cancer tissue samples. Ovarian cancer cell lines exhibited significant binding to collagen type I and laminin which was primarily mediated by β1 integrins. In contrast, ovarian cancer cell binding to fibronectin was mediated by both α5β1 and αvβ3 integrins. Even though mesothelial cells were observed to express fibronectin mRNA and protein, binding of ovarian cancer cells to peritoneal mesothelium was not blocked by neutralizing antibodies to β1 or αvβ3 integrins. These data suggest that functional integrins are commonly expressed by ovarian cancer cells, although they do not appear to mediate ovarian cancer cell implantation onto peritoneal mesothelium. The role that integrins play in the invasion of ovarian cancer cells into the submesothelial ECM deserves further investigation.