Polarization of macrophages in the tumor microenvironment is influenced by EGFR signaling within colon cancer cells
Metrics: PDF 2784 views | HTML 3626 views | ?
Weina Zhang1, Lechuang Chen1, Kai Ma1, Yahui Zhao1, Xianghe Liu1, Yu Wang1, Mei Liu1, Shufang Liang2, Hongxia Zhu1, Ningzhi Xu1,2
1Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P.R. China
Hongxia Zhu, email: email@example.com
Ningzhi Xu, email: firstname.lastname@example.org
Keywords: TAM, colon cancer, tumor microenvironment, EGFR, IGF-1
Received: March 15, 2016 Accepted: September 13, 2016 Published: September 23, 2016
Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4. By contrast, conditioned medium of EGFR knockout colon cancer cells inhibited expression of these M2-related markers and induced macrophage expression of the M1-related markers inducible nitric oxide synthase (iNOS), IL-12, TNF-α and CCR7. EGFR knockout in colon cancer cells inhibited macrophage-induced promotion of xenograft tumor growth. Moreover, colon cancer-derived insulin-like growth factor-1 (IGF-1) increased Arg1 expression, and treatment with the IGF1R inhibitor AG1024 inhibited that increase. These results suggest that inhibition of EGFR signaling in colon cancer cells modulates cytokine secretion (e.g. IGF-1) and prevents M1-to-M2 macrophage polarization, thereby inhibiting cancer cell growth.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.