METASTATIC BEHAVIOR OF HUMAN TUMORS IN CONGENITALLY ATHYMIC NUDE-MICE- INTRINSIC-PROPERTIES OF THE TUMOR-CELLS AND HOST IMMUNE REACTIVITY

Congenitally athymic nude (nu/nu) mice have been used extensively as h osts to study the metastatic properties of xenografted human tumors. I t has not been fully explored to what extent the metastatic behavior o f human tumor xenografts reflects the intrinsic properties of the tumo r cells and to what extent it is influenced artificially by the host. The purpose of the work reported here was to evaluate the potential us efullness of athymic mice for qualitative and quantitative assessment of the intrinsic metastatic properties of human tumor cells. Four huma n melanoma cell lines (A-07, D-12, R-18, U-25) were included in the st udy. Quantitative intradermal and intracranial transplantation assays were used to determine the tumorigenicity and immunogenicity of the ce ll lines. The metastatic behavior of the cell lines was studied by ino culating cells intra-arterially or intravenously (artificial metastase s) or intradermally (spontaneous metastases). The influence of the hos t on the incidence of metastases was assessed by inoculating cells int ravenously in immunologically modified athymic mice. Both the intrader mal and intracranial tumorigenicity differed substantially between the cell lines. The host immune reactivity against heterotransplantation was significantly lower for D-12 than for A-07, R-18 and U-25 cells. T he incidence of metastases was influenced significantly by the host im mune reactivity. The cell lines showed organ-specific metastatic patte rns in athymic mice. The organs of preference were lungs for A-07 and D-12 cells, lymph nodes for R-18 cells, and brain for U-25 cells. The organ-specific metastatic pattern in athymic mice reflected the patter n of distant metastases in the donor patients. In addition, all cell l ines gave rise to metastases in abdominal organ sites, but without org an specificity. The incidence of abdominal metastases was influenced s ignificantly by the tumorigenicity of the cell lines. In conclusion, a thymic mice appear to be excellent hosts for assessment of the organ s pecificity in the metastatic behavior of human tumors. The metastasis frequency of human tumors in athymic mice, however, might be a mislead ing quantitative measure of the intrinsic metastatic propensity of the tumor cells, owing to the cell-line-dependent host immune reactivity. (C) 1995 Wiley-Liss, Inc.