Enhanced metastatic potential of tumor cells harvested from spontaneous metastases of heterogeneous murine tumors.

These studies demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cells populating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random. The tumors used in these studies were the UV-2237 fibrosarcoma, an in vitro cloned line (C-40) from the UV-2237 tumor, and the K-1735 melanoma, all of which are syngeneic to the C3H/HeN (mammary tumor virus-negative) mouse strain; the M5076 reticulum cell sarcoma and the Lewis lung carcinoma 3LL, which are syngeneic to the C57BL/6 mouse strain, were also used. All tumors were implanted sc into the footpads of syngeneic mice, and several resulting spontaneous metastases were isolated and established in culture as individual cell lines. For each tumor system, comparison was made of the ability of parent tumor cells and cells isolated from several spontaneous metastases to produce either experimental or spontaneous metastases. Cells populating spontaneous metastases produced by heterogeneous and poorly metastatic tumors were significantly more metastatic than the cells of their respective parent tumors. In contrast, cells populating metastases produced by previously selected tumors did not differ significantly in metastatic potential from cells populating their parent tumors. In such systems, metastasis appeared to be random.