Selection of 3LL tumor subline resistant to natural effector cells concomitantly selected for increased metastatic potency

Studies were carried out to test whether the selection of 3LL tumor cells resistant to the cytotoxic activity of normal spleen cells will concomitantly select for increased metastatic capacity. A total of 0.5×10⁶ 3LL tumor cells and 50×10⁶ normal spleen cells were admixed and inoculated SC in C57BL/6 mice. This procedure was repeated for eight transplant generations. The tumor cells which were selected in this manner (3LLN) were relatively resistant in vitro to the cytotoxic effect of normal spleen sells. The 3LLN cells were less susceptible than the original 3LL tumor cells to the hybrid resistance mechanisms, as determined by their growth capacity in F1(BALB/c×C57BL/6) or F1(C3H/DiSn×C57BL/6) mice. After three selection generations, 3LLN tumor cells were more efficient in the production of spontaneous lung metastases. These results support our suggestion that natural cell-mediated immunity may be involved in the control of metastatic spread.