Inhibited growth of a reticulum cell sarcoma (M5076) induced in vitro and in vivo by macrophage-activating agents.

The tumor M5076 is highly malignant in vivo; however, in vitro M5076 tumor cells express many of the differentiated characteristics of an activated macrophage. Recently, we reported that this macrophage tumor (M5076) can be induced to cease cellular division following in vitro exposure to macrophage-activating agents, which we felt was due to the induction of terminal differentiation. In the present study, we report that not all macrophage-activating agents halt the proliferation of M5076 tumor cells in vitro, and we present evidence that the treatment of mice bearing M5076 tumor cells with lipopolysaccharide is a highly effective therapeutic modality. Therapy protocols using multiple injections of lipopolysaccharide are capable of prolonging the survival and reducing the metastatic tumor burden of mice with a large tumor burden at the onset of therapy. This indicates that caution should be exercised in the use of M5076 tumors as a test model for chemotherapeutic agents, since the slightest contamination of an experimental drug with lipopolysaccharide would result in spurious positive results.