Macrophage migration inhibitory factor promotes vasculogenic mimicry formation induced by hypoxia via CXCR4/AKT/EMT pathway in human glioblastoma cells

作者：Xing Guo, Shugang Xu, Xiao Gao, Jian Wang, Hao Xue, Zihang Chen, Jinsen Zhang, Xiaofan Guo, Mingyu Qian, Wei Qiu, Gang Li · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.18673 · 被引用次数：58 · 研究领域：Macrophage Migration Inhibitory Factor、Nuclear Receptors and Signaling、Circular RNAs in diseases

// Xing Guo 1 , Shugang Xu 1, 4 , Xiao Gao 1 , Jian Wang 1, 2, 3 , Hao Xue 1 , Zihang Chen 1 , Jinsen Zhang 1 , Xiaofan Guo 1 , Mingyu Qian 1 , Wei Qiu 1 and Gang Li 1, 2 1 Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China 2 Brian Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China 3 Department of Biomedicine, University of Bergen, 5009-Bergen, Norway 4 Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong Province, P.R. China Correspondence to: Gang Li, email: ligangqiluhospital@163.com Keywords: hypoxia, vasculogenic mimicry, MIF, CXCR4, glioblastoma Received: August 24, 2016     Accepted: May 08, 2017     Published: June 27, 2017 ABSTRACT Macrophage migration inhibitory factor (MIF) is over-expressed and secreted in various cancer cells in particular in response to hypoxia. Recent studies have shown that, under hypoxic conditions, glioblastoma (GBM) cells display the ability to drive blood-perfused vasculogenic mimicry (VM). The aim of this study was to investigate the underlying mechanism of MIF in the regulation of hypoxia-induced VM in GBM cells. By analyzing clinical specimens, we observed the co-localization of MIF, C-X-C motif chemokine receptor 4 (CXCR4) and VM in hypoxic regions of gliomas. In vitro , the exposure of GBM cells (U87 and U251) to hypoxia increased the expression of MIF and CXCR4 and induced VMs. Other d...