Selecting, accelerating and suppressing interactions between macrophages and tumor cells.

Abstract

Studies were carried out to test whether thioglycollate-induced macrophages (T-PM phi) exert a selective effect on 3LL tumor cells. One million 3LL tumor cells and 10 X 10(6) thioglycollate-elicited peritoneal macrophages were admixed and inoculated subcutaneously in C57BL/6 mice. This procedure was repeated for a series of 6-15 consecutive transplant generations. After 6 generations, the tumor cells which were selected in this manner (3LLR6) grew faster in vivo and in vitro when admixed with T-PM phi than 3LL cells which were not selected by T-PM phi. However, in vivo, this T-PM phi-mediated acceleration of 3LLR6 tumor growth was followed by tumor rejection and induction of anti-3LL immunity. Intravenous inoculation of T-PM phi enhanced the growth of pulmonary metastases in mice subsequently inoculated intravenously with 3LL cells. Such T-PM phi-mediated augmentation of metastases was not observed with 3LLR6 cells. Homing of 3LL and 3LLR6 cells to the lungs after pretreatment with T-PM phi was similar, indicating that these cells did not differ in their capacity to colonize the lungs but rather in subsequent tumor growth. Additional transplantations of 3LLR6 cells with T-PM phi led, after 9 further transplant generations, to a different tumor cell, 3LLR15, with completely new morphological, tumorigenic and metastatic properties. Unlike the 3LLR6 cells, this variant was not sensitive to the growth promoting effects of T-PM phi. Furthermore, it expressed the H-2K-and H-2D-encoded antigens of the H-2b haplotype, whereas the 3LL and 3LLR6 cells expressed only the H-2D alloantigens. This indicates that macrophages may either exert a selective effect on tumor cells or play a role in the induction of new tumor cells.