摘要
Breast cancer is the most prevalent cancer worldwide,and metastasis is the leading cause of death in cancer patients.Human monocyte chemoattractant protein-1(MCP-1/CCL2)was isolated from the culture supernatants of not only mitogen-activated peripheral blood mononuclear leukocytes but also malignant glioma cells based on its in vitro chemotactic activity toward human monocytes.MCP-1 was subsequently found to be identical to a previously described tumor cell-derived chemotactic factor thought to be responsible for the accumulation of tumor-associated macrophages(TAMs),and it became a candidate target of clinical intervention;however,the role of TAMs in cancer development was still controversial at the time of the discovery of MCP-1.The in vivo role of MCP-1 in cancer progression was first evaluated by examining human cancer tissues,including breast cancers.Positive correlations between the level of MCP-1 production in tumors and the degree of TAM infiltration and cancer progression were established.The contribution of MCP-1 to the growth of primary tumors and metastasis to the lung,bone,and brain was examined in mouse breast cancer models.The results of these studies strongly suggested that MCP-1 is a promoter of breast cancer metastasis to the lung and brain but not bone.Potential mechanisms of MCP-1 production in the breast cancer microenvironment have also been reported.In the present manuscript,we review studies in which the role of MCP-1 in breast cancer development and progression and the mechanisms of its production were examined and attempt to draw a consensus and discuss the potential use of MCP-1 as a biomarker for diagnosis.
