癌症研究
胶质瘤
贝伐单抗
血管生成
医学
缺氧(环境)
肿瘤进展
血管内皮生长因子
基因敲除
下调和上调
间充质干细胞
上皮-间质转换
血管内皮生长因子A
病理
生物
转移
细胞培养
化学
癌症
内科学
化疗
遗传学
生物化学
有机化学
氧气
基因
血管内皮生长因子受体
作者
Hui Xu,Shervin Rahimpour,Cody L. Nesvick,Xu Zhang,Jingyun Ma,Min Zhang,Ge Zhang,Li Wang,Chunzhang Yang,Christopher S. Hong,Anand V. Germanwala,J. Bradley Elder,Abhik Ray‐Chaudhury,Yao Yu,Mark R. Gilbert,Russell R. Lonser,John D. Heiss,Roscoe O. Brady,Ying Mao,Jianhua Qin,Zhengping Zhuang
出处
期刊:Oncotarget
[Impact Journals, LLC]
日期:2015-03-14
卷期号:6 (14): 11882-11893
被引量:68
标识
DOI:10.18632/oncotarget.3592
摘要
Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), can attenuate tumor-associated edema and improve patient symptoms but based on magnetic resonance imaging, is associated with non-enhancing tumor progression and possibly gliosarcoma differentiation. To gain insight into these findings, we investigated the role of hypoxia and epithelial-mesenchymal transition (EMT)-associated proteins in GBM. Tumor markers of hypoxia and EMT were upregulated in bevacizumab-treated tumors from GBM patients compared to untreated counterparts. Exposure of glioma cells to 1% oxygen tension increased cell proliferation, expression of EMT-associated proteins and enhanced cell migration in vitro. These phenotypic changes were significantly attenuated by pharmacologic knockdown of hypoxia-inducible Factor 1α (HIF1α) or HIF2α, indicating that HIFs represent a therapeutic target for mesenchymal GBM cells. These findings provide insights into potential development of novel therapeutic targeting of angiogenesis-specific pathways in GBM.
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