Metastasizing potentials of mouse mammary tumors and their metastases

This in vivo investigation determined the relative potentials of 7 C3H/He and C3Hf/He mammary tumors and their metastases to metastasize spontaneously from intramammary implants. The purpose of the studies was to examine the hypothesis that metastases derive from distinct sub-populations of cells in primary tumors which have specific inheritable characteristics that predispose the cells to form metastases. By serially transplanting, in parallel tests, tissue from autochthonous metastases and tissue from autochthonous primary tumors, the distinction of tumor-cell populations with different metastatic potentials was anticipated. However, the results of the experiments showed that primary tumors and metastases in autochthonous hosts had similar potentials for spontaneous metastasis. Moreover, the primary tumors and the metastases, transplanted as parallel lines through consecutive generations, maintained similar average metastasizing potentials. Changes in metastatic potential which occurred in 3 of the 7 tumors during serial passage appeared in nearly equal transplant generations in the parallel lines of the primary tumor and the metastases. The data suggest that the spontaneous metastases were not derived from a sub-population of cells with inheritable high metastasizing potential, but developed through stochastic events from the average tumor cells that entered the circulation.