CCL5 secreted by luminal B breast cancer cells induces polarization of M2 macrophages through activation of MEK/STAT3 signaling pathway via CCR5.

In humans, breast cancer affects a large number of females and causes a high rate of mortality worldwide. Chemokine (C-C motif) ligand 5 (CCL5) is one of the cytokines that is highly correlated to the invasive and metastatic stages of breast cancer. Our previous study has suggested the prognostic value of CCL5 expression in luminal B (HER2 - ) breast cancer. In this study, CCL5 expression was upregulated or knockdown in a luminal B breast cancer cell line, ZR7530. Further, we elucidated the effects of CCL5 on the differentiation of THP-1 monocytes into M2 macrophages. Overexpression of CCL5 affected THP-1-M2 differentiation and phosphorylation of MEK1/2, ERK1/2, and STAT2 in the cocultivated cell lines. We report that the knockdown of CCR5, a receptor of CCL5 in THP-1, inhibited the effect of ZR7530 in promoting THP-1-M2 differentiation. Furthermore, our data revealed that the inhibition of MEK1/2 and STAT3 in THP-1 cells produced equivalent results similar to those of CCL5 knockdown. In summary, we revealed the role of CCL5 in the polarization of M2 macrophages. Furthermore, we studied its interaction with CCR5 and MEK/STAT3 signaling members. These targets could be used as key regulatory members in human breast cancer therapy.