Relationship between metastatic potential and resistance to natural killer cell-mediated cytotoxicity in three murine tumor systems

The expression of metastatic potential of tumor cells from three different murine tumor systems was correlated with their susceptibility to destruction by NK cells in vivo and in vitro. In the B16 melanoma system, no differences were found in susceptibility to NK-mediated lysis in vitro among the B16-F1 (low metastatic potential), B16-F10^Lr (low metastatic potential), and B16-F10 (high metastatic potential) cell lines. This result was also manifested in vivo by the increase in the incidence of metastases exhibited by all three B16 tumor variants when injected into recipients with low levels of NK cell activity (3-wk- old syngeneic inbred C57BL/6 and beige mice). In the K-1735 melanoma system, cells obtained from different pulmonary metastases were uniformly more metastatic than were cells harvested from the parental tumor. Nonetheless, these cells did not exhibit a uniform pattern of resistance or susceptibility to lysis mediated by NK cells in vitro. In the third tumor system, the UV-2237 fibrosarcoma, cloned lines that differ in their metastatic potential as well as cells obtained from several spontaneous or experimental metastases were all sensitive to NK lysis. In another set of experiments, two variant tumor lines (NK-5 and NK-6) resistant to lysis mediated by NK cells were selected in vitro from the heterogeneous UV-2237 fibrosarcoma. These NK-resistant tumor cells were shown to be highly metastatic in syngeneic inbred C3H^- mice as well as in allogeneic outbred N:NIH(S) nude mice that possessed high levels of NK cell activity. These data indicated that resistance to lysis mediated by NK cells was not a major or sole prerequisite for successful metastasis. Resistance to NK-cell-mediated lysis, however, could enhance metastasis formation by cells that possessed other properties required to complete this process.—JNCI 1981; 66:1183-1190.