Contribution of macrophages to interactions between tumor cells and other tissues assessed in an in vitro system

The modification of the tissues surrounding solid tumors is usually attributed exclusively to interactions between the normal tissues and the cancer cells in the tumor, in spite of the fact that tumors contain many different types of non-cancer cells including macrophages. As an experimental model for some facets of the cellular interactions between tumor and normal tissues, we have assessed the individual contributions of macrophages and cancer cells to the differential inhibition of neural retina (NR) cell aggregation by co-culturing NR cells with small numbers of macrophages or cancer cells alone, as well as with both natural (ascites tumors) and artificial mixtures. Cells from human colonic adenocarcinoma inhibited NR aggregation to a greater extent than normal colon mucosa. Aggregation of NR cells was inhibited by macrophages from mice and rats, and to a greater extent by cancer cell suspensions of mouse Ehrlich and rat Walker 256 lines from spinner culture or in the ascites form. Combinations of macrophages and cancer cells indicated that their inhibitory effects were neither additive nor synergistic. Cell-free media from macrophages and cancer cell cultures were equally effective inhibitors of aggregation. The results suggest that the interaction between a malignant tumor and the surrounding normal tissue can be modified by cancer cells, tumor macrophages and their products.