Cholera toxin-induced alteration of the phenotype and behaviour of an ovarian carcinoma cell line, SR8

Cholera toxin (CT) has been reported to cause a variety of effects on sever al different cell types. Recently, CT has been shown to increase the suscep tibility of ovarian carcinoma cells to cytotoxicity mediated by a variety o f effector cells (natural killer, lymphokine-activated killer cells and tum our-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demo nstrated several effects on a newly established ovarian carcinoma line (SR8 )(1) when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellula r shape, with less cell dispersion than the non-CT treated cells. Cholera t oxin prolonged the population doubling time by approximately 10 h. The CT-t reated SR8 cells exhibited reduced epidermal growth factor receptor express ion (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric anal yses. These changes in morphology and tumour marker expression were reversi ble when CT was removed from the culture. The CT-treated SR8 cells showed r educed capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal x enografts with local invasion in an animal model. Cytogenetic analysis of t he cell line SR8 before and during treatment with CT showed no new clonal r earrangements. The possible mechanisms involved and the influence of CT on the biological behviour of ovarian tumour cells are discussed.