Differences in resistance of metastatic tumor cells and cells from local tumor growth to cytotoxicity of natural killer cells.

Cells from local tumor growth (L-3LL) were compared to metastatic tumor cells (M-3LL) for their susceptibility to the cytotoxicity of natural killer (NK) cells. M-3LL cells were more resistant in vitro to NK cells from normal spleens than were L-3LL cells. A similar phenomenon of relative resistance of metastatic cells to NK activity was found when L-3LL and M-3LL cells were admixed with normal spleen cells and then inoculated into syngeneic mice. Because hybrid resistance was shown to be based on mechanisms that in principle are similar to mechanisms involved in NK activity, we tested the growth of M-3LL and L-3LL cells in semiallogeneic F1 mice. The in vitro effect of NK cells from semiallogeneic mice on M-3LL and L-3LL cells was tested in parallel. In vitro tests showed that irrespective of the haplotype of the spleen cell donors, L-3LL cells were more susceptible to NK activity than were M-3LL cells. In vivo experiments indicated that whereas M-3LL and L-3LL cells grew similarly in syngeneic recipients, M-3LL cells grew far more in F1 mice than did L-3LL cells. Thus metastatic cells are more resistant to NK activity than are cells of the local tumor growth. This relative resistance may determine, among other factors, the metastatic spread and progression of tumor cells.