期刊
ONCOTARGET
卷 6, 期 14, 页码 11882-11893出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3592
关键词
glioblastoma; bevacizumab; epithelial-mesenchymal transition; pathologic angiogenesis; hypoxia-inducible factor
资金
- National Nature Science Foundation of China [11161160552, 91227123]
- Key Projects in the National Science & Technology Pillar Program in the Twelfth Five-Year Plan Period of China [2012BAK02B00, 2012BAK02B03]
- Intramural Research Program at the National Institutes of Health (NIH), National Cancer Institute
- NIH Medical Research Scholars Program - NIH
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 1 alpha (HIF1 alpha) or HIF2 alpha, 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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