Stimulation of proliferation in mixed cultures of mouse tumor cells and nonimmune peritoneal cells. I. Occurrence of stimulation and cyclical variation in tumor cell activity.

Mixtures of mouse tumor cells and resident peritoneal cells (PC) from nonimmune mice frequently incorporated [methyl-3H]thymidine [( 3H]dThd) in culture to a far greater extent than did either cell population alone. With PC-to-tumor cell ratios of 10:1, stimulation indices of up to 21 were recorded. Syngeneic, semisyngeneic, and allogeneic mixtures were active. PC elicited by thioglycollate or proteose-peptone could participate in the reaction. PC from mice injected with Corynebacterium parvum also could do so, provided they were precultured for 48 hours. Normal mouse spleen cells and fibroblasts and human Chang cells were inactive. There was considerable variation between experiments in the extent of stimulation observed, even with the same tumor. When tumors were cloned in vitro, freshly isolated clones differed widely in the extent of stimulation. Individual clones studied over a period of time varied markedly and cyclically in the degree of stimulation they exhibited in mixed cultures. This variation appeared to be unrelated to the density of the cultures from which the clones were obtained, to the base-line incorporation of [3H]dThd by tumor cells alone, or to the frequency of passage in vitro. It is suggested that the cyclical variation may be related to the generation of variant cells, which could be important in tumor progression and metastasis.