MONOCYTE CHEMOATTRACTANT PROTEIN-1 STIMULATES TUMOR NECROSIS AND RECRUITMENT OF MACROPHAGES INTO TUMORS IN TUMOR-BEARING NUDE-MICE - INCREASED GRANULOCYTE AND MACROPHAGE PROGENITORS IN MURINE BONE-MARROW

Monocyte chemoattractant protein-1 (MCP-1) belongs to the newly recogn ized ''chemokine'' superfamily of activation-inducible cytokines. We r eport here that MCP-1 gene-transferred mouse myeloma cells modulate tu mor necrosis in myeloma-bearing nude mice. We established an MCP-1-pro ducing myeloma cell line (X63-MCP-1) by transfection with human MCP-1 cDNA as well as interleukin-8-producing X63 cells (X63 IL-8). Each cel l line showed the same growth characteristics in vitro, and 1x10(7) ce lls per mouse were injected into the peritoneal cavity resulting in th e formation of tumors. Hematologic studies, including peripheral white blood cell counts and differentiation, showed no differences among th e groups. They formed tumors in the same manner, which we observed fro m weeks 2.5 to 9. MCP-1 mice showed more tumor necrosis and infiltrati on of the macrophages into the tissue surrounding the tumor. In situ h ybridization, using a partial cDNA as a probe, showed that macrophages contained MCP-1 mRNA. Bone marrow cell colony-forming assay showed a greater number of both granulocyte and macrophage colonies in MCP-1 mo use femur than in those of controls or interleukin-8 mice. MCP-1 has n o direct stimulatory activity on stem cells, but longer exposure to MC P-1 in vivo might stimulate both granulocyte and macrophage progenitor s and recruitment of macrophages into tumors, and it might explain the antitumor activity of macrophages in tumor-bearing nude mice.