Differential sensitivity of metastatic versus nonmetastatic mammary tumor cells to macrophage-mediated cytostasis

Abstract

Sensitivity to macrophage-mediated cytostasis was determined with 4 tumor cell lines derived from a single, spontaneously arising mouse mammary tumor. Cytostasis was measured in a 48-hour [3H]thymidine-incorporation assay with the use of maleic vinyl ether (pyran) fraction 2 (MVE-2)-elicited peritoneal macrophages as effector cells. Metastatic tumor lines 66 and 410.4 were less sensitive than nonmetastatic lines 67 and 168. Pretreatment of tumor cells with indomethacin for 24 hours before assay increased the cytostatic sensitivity of the metastatic tumor lines but did not affect that of the nonmetastatic tumor lines. Addition of 100 ng lipopolysaccharide (LPS)/ml to the assay mixture of MVE-2-primed macrophages and tumor cells or pretreatment of macrophages with LPS markedly lessened the differences in cytostatic sensitivity among the metastatic and nonmetastatic lines. Pretreatment of tumor cells with indomethacin plus addition of LPS during the effector phase of the assay completely abrogated differences in sensitivity. These results suggest that differences in sensitivity of metastatic versus nonmetastatic tumor cells to macrophage cytostasis are due to both tumor cell (prostaglandin) and effector cell (activation state) factors.