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In vivo isolation of a metastatic tumor cell variant involving selective and nonadaptive processes.

An investigation was done to determine whether spontaneous metastases that develop in a C3H mouse bearing the syngeneic UV-2237 fibrosarcoma are derived from specialized subpopulations of cells or represent an adaptation process to a local (organ) environment. Inbred C3H mice received sc injections of parent tumor and, 9 weeks later, 5 individual pulmonary metastases were harvested and established in culture. Cells from each of these metastases colonized in the lungs of normal recipient mice with significantly greater efficiency than did cells from the parent tumor. Mice received injections iv of cells from a cloned line of UV-2237 that produced few lung metastases. Cells from these metastases did not colonize in the lungs at a dramatically higher rate than did the parent clone. The growth per se of tumor cells into colonies in the lung is not sufficient by itself to endow cells with metastatic properties. The selection in vivo of cells with enhanced lung colonization does not require that the lung be used as a selective organ. A cell variant was selected for enhanced capacity to grow in the peritoneal cavity of normal recipients. This cell line was also found to have a high capacity to colonize in the lungs following introduction into the circulation. It was concluded that the growth of metastases in this murine tumor system was not due to adaptive processes but rather to selection by intrinsic properties of tumor cells.