Effect of Monocyte Chemotactic Cytokine Gene Transfer on Macrophage Infiltration, Growth and Metastatic Behaviour of a Murine Melanoma
Tumor-derived chemotactic factors have been identified and suggested to play a role in the regulation of macrophage infiltration in neoplastic tissues. Aim of this study was to investigate the in vivo relevance of a tumor-derived chemotactic factor molecularly identified as monocyte chemotactic protein (MCP) by gene transfer in a murine melanoma. MCP-producing melanoma clones showed a twofold increase in the percentage of tumor-associated macrophages (TAM) compared to control clones and to the parent line B78/HI. MCP-producing cells exhibited a slower growth rate in vivo with a prolongation of survival time while the in vitro growth rate of melanoma clones was unaffected by MCP gene transfer. Similar differences between MCP-producing and control cells, in terms of macrophage infiltration and growth rate, were detected after implantation in athymic mice. After inoculation of small cell numbers (100 cells/mouse), MCP-producing cells were slightly, but significantly, more tumorigenic. Finally the metastatic behaviour of MCP-producing and control clones was studied: after i.v. injection MCP-expressing cells were more metastatic than control cells in terms of lung involvement and of the occurrence of extrapulmonary lesions. These results demonstrate that a tumor-derived chemotactic cytokine can indeed play a role in the regulation of mononuclear phagocyte recruitment in neoplastic tissues.