title: Iron participated in breast cancer chemoresistance by reinforcing IL-6 paracrine loop.
abstract: Chemotherapeutic efficacy is also regulated by the tumor microenvironment. IL-6 produced by TAMs and downstream IL-6/STAT3 signaling pathway is central regulator in chemotherapeutic response. The M2-like phenotype of TAMs is characterized by elevated iron uptake. Whether iron participates in chemo-resistance need to be elucidated. In the present study, we found that IL-6 participated in breast cancer chemoresistance. Local IL-6 paracrine loop acted as exogenous IL-6 rich niche for chemo-sensitive breast cancer cells, leading to de novo acquired drug resistance. Furthermore, Iron reinforced the IL-6 paracrine loop between TAMs and tumor cells resulting in enhanced chemo-resistance. Targeting iron metabolism could disturb the reciprocal interaction between tumor cells and TAMs, breaking the local IL-6 rich niche and blocking IL-6 signaling pathway, which could be promising strategy to overcome chemo-resistance.
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China. Electronic address: pingliu@sjtu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China; School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Lisa X
authors.initials: LX
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001940:Breast / Q000187:drug effects / Q000276:immunology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D007501:Iron / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008807:Mice, Inbred BALB C; D019899:Paracrine Communication / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D007501:Iron
keywords: Chemoresistance; IL-6; Iron; Tumor associated macrophage