A causal role was recently attributed to
inflammation in many malignant diseases, including
breast cancer. The different inflammatory mediators that are involved in this disease include cells,
cytokines and
chemokines. Of these, many studies have addressed the involvement and roles of the inflammatory
chemokines CCL2 (MCP-1) and CCL5 (
RANTES) in breast
malignancy. While minimally expressed by normal breast epithelial duct cells, both
chemokines are highly expressed by
breast tumor cells at primary
tumor sites, indicating that CCL2 and CCL5 expression is acquired in the course of malignant transformation, and suggesting that the two
chemokines play a role in
breast cancer development and/or progression. Supporting this possibility are findings showing significant associations between CCL2 and CCL5 and more advanced disease course and progression. Furthermore, studies in animal model systems have shown active and causative roles for the two
chemokines in this disease. In line with the
tumor-promoting roles of CCL2 and CCL5 in
breast cancer, the two
chemokines were shown to mediate many types of
tumor-promoting cross-talks between the
tumor cells and cells of the tumor microenvironment: (1) they shift the balance at the
tumor site between different leukocyte cell types by increasing the presence of deleterious tumor-associated macrophages (TAM) and inhibiting potential anti-
tumor T cell activities; (2) of the two
chemokines, mainly CCL2 promotes angiogenesis; (3) CCL2 and CCL5 which are expressed by cells of the tumor microenvironment osteoblasts and mesenchymal stem cells play a role in breast metastatic processes. In addition, both
chemokines act directly on the
tumor cells to promote their pro-
malignancy phenotype, by increasing their migratory and invasion-related properties. Together, the overall current information suggests that CCL2 and CCL5 are inflammatory mediators with pro-
malignancy activities in
breast cancer, and that they should be considered as potential therapeutic targets for the limitation of this disease.