Oncotarget

Research Papers:

M2-like tumor-associated macrophages drive vasculogenic mimicry through amplification of IL-6 expression in glioma cells

Lin Zhang, Yangyang Xu, Jintang Sun, Weiliang Chen, Lei Zhao, Chao Ma, Qingjie Wang, Jia Sun, Bin Huang, Yun Zhang, Xingang Li and Xun Qu _

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Oncotarget. 2017; 8:819-832. https://doi.org/10.18632/oncotarget.13661

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Abstract

Lin Zhang1,3, Yangyang Xu2, Jintang Sun1,3, Weiliang Chen2, Lei Zhao1,3, Chao Ma1,3, Qingjie Wang1,3, Jia Sun1,3, Bin Huang2, Yun Zhang3, Xingang Li2, Xun Qu1,3

1Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, P.R. China

2Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, P.R. China

3Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, School of Medicine, Shandong University, Jinan, P.R. China

Correspondence to:

Xingang Li, email: [email protected]

Xun Qu, email: [email protected]

Keywords: macrophages, glioma, vasculogenic mimicry, IL-6, PKC

Received: August 02, 2016     Accepted: November 15, 2016     Published: November 26, 2016

ABSTRACT

Vasculogenic mimicry (VM) has offered a new horizon for understanding tumor angiogenesis, but the mechanisms of VM in glioma progression have not been studied explicitly until now. As a significant component of immune infiltration in tumor microenvironment, macrophages have been demonstrated to play an important role in tumor growth and angiogenesis. However, whether macrophages could play a potential key role in glioma VM is still poorly understood. Herein we reported that both VM and CD163+ cells were associated with WHO grade and reduced patient survival, and VM channel counting was correlated to the number of infiltrated CD163+ cells in glioma specimens. In vitro studies of glioma cell lines implicated that M2-like macrophages (M2) promoted glioma VM. We found that conditional medium derived from M2 amplified IL-6 expression in glioma cells. Furthermore, our data indicated that IL-6 could promote glioma VM, as blocking IL-6 with neutralizing antibodies abrogated M2-mediated VM enhancement. In addition, the potent PKC inhibitor bisindolylmaleimide I could prevent M2-induced IL-6 upregulation and further inhibited glioma VM facilitation. Taken together, our results suggested that M2-like macrophages drove glioma VM through amplifying IL-6 secretion in glioma cells via PKC pathway.


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