IL-10 secreted by M2 macrophage promoted tumorigenesis through interaction with JAK2 in glioma

Abstract

// Ling Qi 1 , Hongquan Yu 2 , Yu Zhang 2 , Donghai Zhao 1 , Peng Lv 1 , Yue Zhong 3 , Ye Xu 4 1 The Department of Pathology, Jilin Medical University, Jilin 132013, PR China 2 The Department of Neurosurgery, First Affiliated Hospital of Jilin University, Jilin 130021, PR China 3 The Department of Science and Technology, Jilin Medical University, Jilin 132013, PR China 4 The Medical Research Laboratory, Jilin Medical University, Jilin 132013, PR China Correspondence to: Yue Zhong, email: yuezhong_DST@126.com Ye Xu, email: xuye_mpc@126.com Keywords: glioma, M2 macrophage, proliferation, IL-10, JAK2/STAT3 Received: July 25, 2016      Accepted: September 22, 2016      Published: September 28, 2016 ABSTRACT M2 tumor-associated macrophage has been found to play a supportive role in the progression of glioma. The underlying mechanism, nevertheless, has been largely unknown. In our study, to investigate how M2 macrophage played role in glioma, firstly we’ve analyzed the clinicopathological significance of M2 macrophage existence on clinical tissues of glioma using detection of CD163 expression with immunohistochemistry. Then, we’ve artificially induced M2 macrophage from human monocyte cell line THP-1, followed by co-culture with glioma cell lines in vitro . It was found that M2 macrophage was shown to be markedly distributed in glioma relative to paired normal control; and high prevalence of M2 macrophage was significantly associated with poorer overall survival and tumor progression. Moreover, M2 macrophage was found to be able to promote the growth in vitro and tumorigenesis in vivo in xenografted mice model. Mechanistically, it is IL-10 from M2 macrophage that was shown to promote proliferation, dependent on activation of JAK2/STAT3 pathway. Further, IL-10 was found to be able to interact with JAK2 in glioma cells. Taking together, we for the first time found that IL-10 from M2 macrophage promoted proliferation of glioma through interaction with JAK2; thereby activating the JAK2/STAT3 pathway, indicative of IL-10 could be used as a therapeutic target in the curing of glioma.