Many solid tumors are characterized by macrophage infiltration, which results, to a large extent, from the recruitment of peripheral monocytes. The recruitment of monocytes is thought to be induced by the generation of chemoattractants by tumor cells. Since the last review we demonstrated that there was is a strict relationship between the synthesis of the monocyte chemoattractant protein-1 (MCP-l) and the capacity of bone-derived tumor cells to stimulate monocyte migration in vitro. It has not been determined whether the presence of tumor associated macrophages ultimately enhances or inhibits tumor growth. Although monocytes/macrophages have the potential to eradicate tumors, paradoxically, many solid tumors grow in the presence of a dense macrophage infiltrate. Interestingly, macrophages have the capacity to produce growth stimulating factors/cytokines as well as factors/cytokines that can inhibit tumor growth. -Thus, the specific factors/cytokines produced by tumor associated macrophages in situ may ultimately determine the affect that macrophages have on tumor growth in vivo. The studies outlined in this proposal should determine if MCP-1 is expressed by human osteogenic sarcomas and other tumors in vivo, in an immunodeficient mouse model. These studies will determine if the expression of MCP-1 is responsible for the presence of tumor associated macrophages frequently seen in these tumors in vivo. In addition, the production of growth regulating factors/cytokines by tumor associated macrophages will be examined in situ.
