Altered adhesion properties and alpha V integrin expression in a cisplatin-resistant human ovarian carcinoma cell line

In order to elucidate the mechanisms underlying the development of chemoresistance in ovarian cancer, we have previously established the IGROV1-R10 cisplatin-resistant cell line by mimicking a clinical protocol of drug administration on IGROV1 human ovarian carcinoma cells. Both IGROV1 and IGROV1-R10 cells were able to grow as a monolayer and to release cell clusters into the medium. However, IGROV1-R10 cells exhibited an enhanced capacity to detach from the monolayer as compared to the parental cells. When substrate adhesion was prevented, IGROV1-R10 cells were able to survive and to proliferate as cell clusters, even at a low cell density, whereas IGROV1 cells massively died. To explore the underlying mechanisms, we have been interested in a-v integrins, which have been implicated in some aspects of ovarian cancer biology. Both IGROV1 and IGROV1-R10 adherent cells expressed alphav beta3 integrin. During cell growth, alphav beta5 integrin accumulated at the surface of a majority of IGROV1-R10 cells from the monolayer, whereas only a faint expression of this integrin was observed in a minority of IGROV1 cells. The growth of IGROV1-R10 cells, but not of IGROV1 cells, was partly inhibited by a specific alphav beta5-blocking antibody suggesting that alphav beta5 integrin contributed to IGROV1-R10 cell proliferation. (C) 2002 Wiley-Liss, Inc.