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 several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine-activated killer cells and tumour-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated 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 cellular shape, with less cell dispersion than the non-CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT-treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT-treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behaviour of ovarian tumour cells are discussed.
Han
X
X
United Medical and Dental Schools, Department of Obstetrics and Gynaecology, St Thomas' and Guy's Hospital, London, UK.
Papadopoulos
A J
AJ
Jones
T
T
Devaja
O
O
Raju
K S
KS
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D003470:Culture Media / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C106882:CA602 antigen; D003470:Culture Media; D002772:Cholera Toxin; D066246:ErbB Receptors