Tumor-associated macrophages secrete CC-chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

Li, Dongbo; Ji, Hongfei; Niu, Xingjian; Yin, Lei; Wang, Yiran; Gu, Yucui; Wang, Jinlu; Zhou, Xiaoping; Zhang, Han; Zhang, Qingyuan

We have shown that CCL2 is associated with endocrine resistance in MCF7 and T47D cell lines. As the PI3K/Akt/mTOR signaling pathway is a classic pathway regulating cell proliferation, apoptosis, and endocrine resistance, we investigated the effect of CCL2 on the activation of this pathway. When MCF7 cells were treated with 100 nmol/L CCL2, phosphorylation of Akt and mTOR was significantly increased. Adding CM of MR to MCF7 cells also activated the PI3K/Akt/mTOR signaling pathway. When MR was treated with 300 nmol/L Bindarit (a CCL2 synthesis inhibitor), the ability of the CM (MR + Bindarit) to increase the levels of phosphorylated Akt and mTOR was weakened ( Figure 2G ). These results suggest that TAM promote endocrine resistance in breast cancer cells partly by secreting CCL2, which then activates the PI3K/Akt/ mTOR pathway.