Successful heterotransplantation of human colon cancer cells to athymic animals is related to tumor cell differentiation and growth kinetics and to host natural killer cell activity.

Six established human colon carcinoma cell lines with distinct degrees of cell differentiation were inoculated into infant (less than 4 weeks) and adult (greater than 8 weeks) nude rats. The most differentiated tumor cells (group I) had nearly a 100% rate of tumor takes whether inoculated subcutaneously, intraperitoneally, or intracerebrally into adult rats; subcutaneous growth continued unabated for a 120-day observation period. Cells with intermediate differentiation (group II) had nearly an 80% incidence in tumor takes when injected subcutaneously and 14-60% when injected intraperitoneally. Subcutaneous growth continued only for about 30 days, after which time growth declined, and tumors regressed completely. Intracerebral inoculations of group II cells resulted in 64-83% tumor takes. Subcutaneous injections of cells from groups I and II into 5- to 10-day-old rats resulted in 100% tumor takes; tumors induced by group II did not regress, and after about 60 days reached volumes comparable to those originated by cells from group I. No tumors developed when cells from group III (undifferentiated) were injected either subcutaneously or intraperitoneally (and even intravenously) into adult rats. Only when the intracerebral route was employed was there a 60-71% incidence of tumor takes. Also, for one of the cell lines in this group, subcutaneous injection into infant rats resulted in 100% tumor takes. NK cell activity of infant rats against all of the colon cells (measured by the 51Cr release assay) was negligible; in adult rats, the activity varied according to the cell type, being usually highest against the less differentiated tumors. Our data on the incidence of tumor takes, and on the dynamics of tumor growth and decline suggest that successful heterotransplantation of human colon carcinoma cells into nude rats depends on the activity of host NK cells. In turn, this activity seems related to the degree of cell differentiation and the growth kinetics of the xenografted tumor cells. These observations highlight important differences in biological characteristics of human colon carcinoma with important implications for their intrinsic ability to grow and metastasize, and, possibly, their response to biological response modifiers.