Hepatocyte growth factor stimulates motility, chemotaxis and mitogenesis in ovarian carcinoma cells expressing high levels of c-met

Abstract

A proportion of ovarian carcinomas markedly overexpress the proto- oncogene c-met, which encodes the receptor for hepatocyte growth factor (HGF). HGF may either stimulate or inhibit the multiplication of its target cells, and may also promote motogenesis and morphogenesis. In this study, we established that the ovarian carcinoma-derived cell-line SK-OV-3 expressed about 20-fold higher levels of c-met protein than are expressed by a second line, CHI. This enabled us to test functional consequences of high-level expression of c-met in ovarian carcinoma cells. The addition of HGF to attached cultures of SK-OV-3 cells caused a change to a motile phenotype, that was evident after 4-6 hr and affected essentially all of the cells by 24 hr. When HGF was placed in the lower compartment of a migration chamber, it induced a 17-fold increase in the migration of SK-OV-3 cells to the lower surface of the filter. Finally, HGF stimulated the incorporation of [3H]- thymidine by cultures of SK-OV-3 cells incubated in medium containing either low (0.2%) or full (10%) FCS. None of these responses were obtained when HGF was added to CHI cells. We conclude that high levels of c-met expression in ovarian cancer cells may lead to a range of responses to HGF that would promote tumour growth and dissemination.