CD44 and beta 1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins

Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells that line the peritoneal cavity. The aim of this stud y was to identify the cell-matrix interactions that mediate ovarian carcino ma cell migration toward components of the mesothelial cell-associated extr acellular matrix. The human ovarian carcinoma cell lines NIH:OVCAR5 and SKO V3 were analyzed by flow cytometry for the expression of cell surface recep tors. The ability of those receptors to mediate ovarian carcinoma cell migr ation toward fibronectin, type IV collagen, and laminin was determined. A m onoclonal antibody against the beta1 integrin subunit abrogated the migrati on of both cell lines toward the extracellular matrix proteins. Blocking an tibodies against alpha integrin subunits suggest that ovarian carcinoma cel l migration toward fibronectin is primarily mediated by the proportional to 5 beta1 integrin, type IV collagen by the proportional to2 beta1 integrin, and laminin by the proportional to6 beta1 integrin. These results suggest t hat ovarian carcinoma cell migration is regulated by multiple beta1 integri n-matrix interactions. Significant reduction of cell migration was observed with a monoclonal antibody against CD44 that blocks the hyaluronan-binding site of CD44, but not with an antibody that binds at an alternate site on CD44. Intact hyaluronan and/or hyaluronan oligomers also inhibited cell mig ration, suggesting that the CD44-hyaluronan interaction provides an integri n-independent mechanism of control for ovarian carcinoma cell migration. Th ese results suggest that ovarian carcinoma cell migration is regulated by b oth integrin-dependent mechanisms, involving the interaction of beta1 integ rins with extracellular matrix proteins, and an integrin-independent mechan ism that involves the interaction of CD44 and hyaluronan.