Comparative studies on the quantitative analysis of experimental metastatic capacity.

The purpose of these studies was to establish a procedure for determining the relative experimental metastatic potential of unrelated murine tumors. We used three tumors (the B16-F10 melanoma, which is syngeneic to the C57BL/6N mouse, and the K-1735 melanoma and the UV-2237 fibrosarcoma, which are syngeneic to the C3H/HeN mouse). Various numbers of tumor cells were injected into normal or immunosuppressed syngeneic recipients and into 3-week-old BALB/c nude mice. At appropriate intervals, the recipient mice were killed, and the metastatic burden was determined. The number of experimental metastases was not linearly correlated with cell input. Thus, simply comparing the incidence of metastasis resulting from the injection of one predetermined dose of tumor cells did not allow for determination of their relative metastatic capacities. More reproducible and meaningful results were obtained by introducing increasing numbers of viable tumor cells admixed with a constant number of nontumorigenic (X-irradiated) tumor cells serving as carrier. The incidence of metastasis by few or many injected cells is influenced by host factors such as immune status, and therefore determinations of the true metastatic nature of any given tumor necessitate the choice of an appropriate recipient.