Congenital athymic mice are frequently used as in vivo culture systems for establishing human neoplastic cells for a number of different types of studies. This study reports that growth of human tumor cells in athymic mice may alter the biological and immunological properties of the cell line. Human colon tumor cell lines HCT-8R and HT-29 were grown in nude mice and explanted back into culture. These nude mouse-derived sublines were designated HCT-8R Nu1 and HT-29 Nu1. The nude mouse tumor-forming doses of the Nu1 sublines were 10- to 100-fold lower than the original cell lines. Using monospecific antibodies to carcinoembryonic antigen in a complement-dependent 51Cr cytotoxicity assay, the Nu1 sublines were markedly more resistant to lysis than were the original cell lines. A quantitative 125I-anti carcinoembryonic antigen-binding assay revealed no significant difference in carcinoembryonic antigen on the surface of original cell lines and the Nu1 sublines. Nu1 sublines were also more resistant than the original cell lines to complement-dependent lysis by heterologous antisera against viable HCT-8R and HT-29 cells. Lack of correlation was observed between adsorption of anti-HCT-8R antibodies by HCT-8R and HCT-8R Nu1 and their respective susceptibility to antibody lysis. These results suggest that the nude mouse exerts some immunological and nonimmunological influences on xenografted tumor cells resulting in a cell population that is more tumorigenic and more resistant to antibody lysis. These modifications in the properties of Nu1 sublines do not appear to be related to changes in antigenic expression per se on the cell surface.
This study was supported by Contract NO1 CB 64073 from the National Cancer Institute of the United States Department of Health Education and Welfare.