Tumor subpopulation interactions in metastasis.

Subpopulations isolated from a single mouse mammary tumor differ in ability to metastasize when tested independently in normal, syngeneic mice. The presence of a metastatic subpopulation, however, enabled relatively nonmetastatic subpopulations to metastasize. Tumor subpopulation 67 did not form metastatic nodules after intravenous injection of 3 X 10(6) cells. If injected with 1 X 10(4) cells of the metastatic subpopulation 410.4, colony-forming tumor 67 cells, as well as 410.4 cells, were found in the resulting lung nodules. Mice bearing subcutaneous implants of subpopulation 168 tumors and which were injected intravenously with saline or 1 X 10(4) of subpopulation 168 cells did not develop metastases. The intravenous injection of 1 X 10(4) of subpopulation 410.4 cells into mice bearing subcutaneously subpopulation 168 tumors resulted in lung nodules consisting of colony-forming 168 as well as 410.4 cells. Thus, the simultaneous presence of metastatic and nonmetastatic subpopulations can result in metastatic nodules containing the nonmetastatic subpopulation.