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

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

doi:10.18632/oncotarget.13661

Lin Zhang, Yangyang Xu + Show 10 more

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https://doi.org/10.18632/oncotarget.13661

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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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Gliomas are a heterogeneous group of neoplasms and constitute approximately 50% of primary brain tumor [1], the most common being the highly malignant glioblastoma [2]
Our results suggested that M2-like macrophages drove glioma Vasculogenic mimicry (VM) through amplifying IL-6 secretion in glioma cells via PKC pathway
To investigate whether the density of M2-like tumor-associated macrophages (TAMs) correlated with the VM level in human glioma, we detected the expression of CD163, CD31 and PAS in 87 human glioma specimens by immunochemical staining

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Introduction

Gliomas are a heterogeneous group of neoplasms and constitute approximately 50% of primary brain tumor [1], the most common being the highly malignant glioblastoma [2]. Despite therapeutic options have improved, the median survival among patients with glioblastoma is only 14.6 months [3]. As glioblastomas are highly vascularized tumors [4], anti-angiogenic therapies targeting endothelial cells have received much attention and investigation [5]. The conventional anti-angiogenic therapy, which seemed promising initially, shows transitory and incomplete efficacy [6,7,8,9]. These studies indicated that there may be other blood supply forms in tumor tissues. As an alternative to conventional antiangiogenic therapy, the identification of molecules and signaling pathways relating to VM may offer potential therapeutic targets to improve treatment [14]

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