Importance of chemokine (CC-motif) ligand 2 in breast cancer.

Breast cancer is the leading cause of cancer-related death in women in the United States. Chemokine (CC-motif) ligand 2 (CCL2), an inflammatory cytokine and chemokine, is highly expressed within the tumor and stromal cell populations and has been associated with enhanced tumorigenesis. In breast cancer patients, CCL2 has been correlated with high tumor grade and has been shown to have significant prognostic value for relapse-free survival. CCL2 likely exerts its pro-tumorigenic effects through recruitment of tumor-associated macrophages (TAMs); TAMs promote a tumorigenic microenvironment through the induction of growth enhancers, angiogenic factors and inflammatory mediators. CCL2 may also stimulate angiogenesis independently of TAM recruitment as it is closely associated with several endothelial cell growth factors. Additionally, CCL2 has been implicated in several processes leading to metastatic establishment including the development of bone metastasis. It has also been reported to directly upregulate pro-tumorigenic inflammatory mediators, including regulated upon activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor-alpha (TNF-α). While there is emerging support for a tumor promoting role of CCL2 in breast cancer, additional research is required before CCL2 can be decisively established as a prognostic factor and/or treatment target in breast cancer.