Human tumor xenografts transplanted under the renal capsule of conventional mice. Growth rates and host immune response.

The growth of 29 different human tumor lines under the renal capsule of immunocompetent mice was investigated. The tumors, previously established in athymic mice, included malignant melanomas, colon carcinomas, soft-tissue sarcomas, lung cancers and a mammary carcinoma. The growth rates of 17 tumors, measured repeatedly over a period of several years, were highly reproducible. The different grafts exhibited distinctly different and individual growth rates for up to 6 days. In animals pretreated with an immunosuppressive dose of cyclophosphamide, the growth rate was the same as in non-pretreated animals, but the growth continued for several more days. In the case of 9 different grafts, the subrenal growth rates were compared with those observed when the same tumors were growing subcutaneously in athymic, nude mice. The relative growth rates of the different tumors were practically the same in the two systems. The results indicate that the growth conditions under the renal capsule permit the grafts to express their inherent growth potentials and that the subrenal grafts do not represent a selected sub-population of the tumor cells. The extent of infiltration of the grafts by mouse inflammatory cells was measured by flow cytometry on single-cell suspension as well as by quantitative analysis of serial histological sections. In most cases the mouse cells occupied 15-25% of the total graft volume on day 6. The results indicate that the effect of mouse cell infiltration on the growth of established tumor lines is slight and that it is unnecessary to use athymic mice as host animals when testing new investigational drugs by the SRC assay. The use of established tumor lines in the SRC assay in immunocompetent mice may be useful also in the study of factors influencing the anti-cancer activity of current drugs.