C/EBPβ promotes angiogenesis through secretion of IL‐6, which is inhibited by genistein, in EGFRvIII‐positive glioblastoma. Issue 11 (26th November 2014)

• Record Type: Journal Article
• Authors: Liu, Xujie; Liu, Kaiyu; Qin, Jiazhen; Hao, Limin; Li, Xiaoxia; Liu, Yinan; Zhang, Xiaoyan; Liu, Xiuxiu; Li, Peng; Han, Shuo; Mao, Zebin; Shen, Li
• Is Part Of: International journal of cancer. Volume 136:Issue 11(2015:Jun. 01)
• Page Start: 2524
• Page End: 2534
• Publication Date: 2014-11-26
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29319
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To study the mechanisms underlying the IL‐6‐promoted angiogenic microenvironment in EGFRvIII‐positive glioblastoma, VEGF expression in EGFRvIII‐positive/negative tumors was determined by optical molecular imaging. Next, the HUVEC tube formation assay, Western blot, qPCR, RNA silencing, chromatin immunoprecipitation, luciferase reporter and ELISA assays were performed to examine the role of IL‐6 and C/EBPβ in the formation of the angiogenic microenvironment in EGFRvIII‐positive tumors. Finally, <italic>in vitro</italic> and <italic>in vivo</italic> genistein treatment experiments were conducted to challenge the interaction between the IL‐6 promoter and C/EBPβ. Optical imaging revealed greater VEGF expression in EGFRvIII‐positive tumor‐bearing mice, suggesting an angiogenic microenvironment. <italic>In vitro</italic> experiments demonstrated that C/EBPβ‐mediated regulation of IL‐6 was indispensable for maintenance of this angiogenic microenvironment. In contrast, genistein‐mediated upregulation of CHOP impeded C/EBPβ interaction with the <italic>IL‐6</italic> promoter, thus disturbing the angiogenic microenvironment. This more malignant microenvironment in EGFRvIII glioblastoma is generated, at least in part, by greater VEGF, IL‐6 and C/EBPβ expression. Interaction of C/EBPβ with the IL‐6 promoter maintains this angiogenic microenvironment, while disturbance of this dynamically balanced interaction inhibits EGFRvIII tumor proliferation by reducing both VEGF and IL‐6 expression.</p> </abstract>