Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression.

摘要: Although several CXC chemokines have been shown to induce angiogenesis and play roles in tumor growth, date, no member of the CC chemokine family has reported a direct role angiogenesis. Here we report that chemokine, monocyte chemotactic protein 1 (MCP-1), induced chemotaxis human endothelial cells at nanomolar concentrations. This response was inhibited by monoclonal antibody MCP-1. MCP-1 also formation blood vessels vivo as assessed chick chorioallantoic membrane matrigel plug assays. As expected, angiogenic accompanied an inflammatory response. With use rat aortic sprouting assay absence leukocytic infiltrates, ruled out possibility effect depended on leukocyte products. Moreover, consistent with expression CCR2, receptor for MCP-1, cells. Assessment supernatant from breast carcinoma cell line demonstrated production Treatment immunodeficient mice bearing neutralizing resulted significant increases survival inhibition growth lung micrometastases. Taken together, our data indicate can act mediator is abundantly produced some tumors, it directly contribute progression. Therefore, therapy employing antagonists combination other inhibitors may achieve more comprehensive growth.