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

CD163 expression was higher and M2 polarization was more significant in MR than in MS ( Figure 1B,C) . These observations indicate that macrophages can be polarized to assume different phenotypes in different microenvironments. Figure 2B ). Thus, we conclude that CCL2 is associated with endocrine resistance promoted by TAM. Two hormone receptor-positive cell lines, MCF7 and T47D, were selected to test the effect of CCL2. We confirmed that CCR2, the receptor of CCL2, was expressed in both cell lines ( Figure S1 ). CCL2 (100 nm/mL) was added to the two cell lines and the cells were cultured for 24 hours. Subsequently, tamoxifen (5 μmol/L) was added to all four groups (MCF7, MCF7+CCL2, T47D, and T47D+CCL2) and the cells were cultured for 24 hours. Cell viability was assessed using the CCK-8 assay ( Figure 2C,D) . The four groups were also analyzed by flow cytometry to detect apoptosis ( Figure 2E ,F). We found that CCL2 promotes endocrine resistance and reduces apoptotic proportion in the two hormone receptor-positive cell lines.