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

Tumor-associated macrophages can adjust their phenotype and function in response to local cues provided by the TME. 49 Crosstalk between TAM and cancer cells is complex and involves exosomes, cytokines, and metabolites. [50] [51] [52] In the present study, we focused on the cytokine CCL2 secreted by macrophages and TA B L E 1 Univariate and multivariate analyses of clinicopathological features associated with PFS of patients with hormone receptor-positive breast cancer examined its role in the endocrine resistance of breast cancer cells. We found that CCL2 activates the PI3K/Akt/mTOR pathway, which is a classical endocrine resistance pathway. However, the direct mechanism by which CCL2 activates this pathway was not determined. Another limitation of the present study was that due to the long culture time of drug-resistant cell lines, the effects of endocrine-resistant and -sensitive T47D cell lines on macrophages could not be repeated.