Abstract
Macrophages are one of the most abundant leukocyte populations infiltrating tumor tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989, we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from culture supernatants of mitogen-activated peripheral blood mononuclear cells and tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the previously described lymphocyte-derived chemotactic factor or tumor-derived chemotactic factor, and greatly contributes to the recruitment of blood monocytes into sites of inflammatory responses and tumors. Because in vitro-cultured tumor cells often produce significant amounts of MCP-1, tumor cells are considered to be the main source of MCP-1. However, various non-tumor cells in the tumor stroma also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo have provided evidence that MCP-1 production in tumors is a consequence of complex interactions between tumor cells and non-tumor cells and that both tumor cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1 production was once considered to be a part of host defense against tumors, it is now believed to regulate the vicious cycle between tumor cells and macrophages that promotes the progression of tumors.
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Acknowledgements
I am grateful to Drs Hideo Hayashi, Edward J Leonard, Kouji Matsushima and Joost J Oppenheim for their invaluable input during my studies on inflammation. I am also grateful to Drs Naoya Yuhki, Shuji Tanaka and Ettore Appella, and Ms Elizabeth A Robinson for their critical collaborations for the identification and cloning of MCP-1, and to Dr Ji Ming Wang and the members of the Laboratory of Molecular Immunoregulation, NCI, for their discussion and support.
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Yoshimura, T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?. Cell Mol Immunol 15, 335β345 (2018). https://doi.org/10.1038/cmi.2017.135
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DOI: https://doi.org/10.1038/cmi.2017.135
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