IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor
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Lechuang Chen1, Shuren Wang1, Yu Wang1, Weina Zhang1, Kai Ma1, Chenfei Hu1, Hongxia Zhu1, Shufang Liang2, Mei Liu1 and Ningzhi Xu1,2
1Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
Mei Liu, email: [email protected]
Ningzhi Xu, email: [email protected]
Keywords: macrophages; polarization; colon cancer; IL-6; animal model
Received: August 02, 2017 Accepted: February 21, 2018 Published: April 03, 2018
Macrophages play a crucial role in tumorigenesis depending upon the phenotype of macrophages found in tumor microenvironments. To date, how the tumor microenvironment affects the phenotypes of macrophages is not yet fully understood. In this study, we constructed a NIH3T3/Src cell line stably overexpresses the Src protein and found that conditioned medium from this cell line was able to induce polarization towards the M2 phenotype in primary bone marrow-derived macrophages (BMDM) and Ana-1 macrophages. Further investigation revealed that IL-6 produced by NIH3T3/Src cells plays a key role in M2 polarization. During the development of colorectal cancer in C57BL/6J-ApcMin/+ mice, increased IL-6 secretion in the interstitial fluid of the colorectal tissues was observed. Furthermore, tumorigenesis in IL-6tm1Kopf mice treated with AOM-DSS, an IL-6 knockout mouse strain, was significantly inhibited compared with the control group, suggesting the important role of IL-6 in promoting tumorigenicity. Our findings identify the target molecules and proinflammatory cytokines responsible for promoting polarization towards the M2 phenotype in macrophages present in tumor microenvironment, which may be useful for the design of novel therapeutic strategies for colorectal cancer.
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