Inhibition of cellular division of a murine macrophage tumor by macrophage-activating agents.

Although the murine reticulum cell sarcoma M5076 is highly malignant in vivo, in vitro it displays many of the functional characteristics of an activated macrophage, such as phagocytosis and tumor cytotoxicity. This study was designed to determine what effect macrophage-activating agents would have on the function and growth of M5076 cells. Exposure of M5076 tumor cells to substances that activate normal macrophages to the tumoricidal state rapidly and irreversibly induced cessation of cellular division. The treated tumor cells, however, retained the same characteristics as those of untreated M5076 cells in vitro with respect to viability and the activated macrophage functions of phagocytosis and tumor cytotoxicity. Even after a short exposure to lipopolysaccharide, the ability of M5076 cells, injected i.v. into syngeneic mice, to form tumor nodules was greatly reduced. These results indicate that a highly malignant tumor of macrophage origin, M5076, can be induced to cease cellular division while retaining the functional attributes of an activated macrophage. We speculate that the exposure of M5076 to macrophage-activating agents results in the induction of terminal differentiation of this tumor.