CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia
Language: 
English
Abstract: 

BACKGROUND: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. METHODS: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated. Bioinformatics analysis was performed to reveal the potential functional roles of CDH5 in glioblastoma multiforme. Gene knockdown induced by short hairpin RNA, chromatin immunoprecipitation analysis, and a vasculogenic tube formation assay were performed to investigate the relationships among hypoxia, CDH5 expression level, and angiogenesis. RESULTS: CDH5 was overexpressed in gliomas, correlated with tumor grades, and was an independent adverse prognostic predictor for glioblastoma multiforme patients. CDH5 was specifically activated in GSCs but not in non-GSCs or neural stem cells, and CDH5(+) cells could produce xenografts in immunocompromised mice. Bioinformatics analysis demonstrated that CDH5 might interact directly with hypoxia-inducible factor (HIF)2?. CDH5 expression was significantly upregulated in GSCs, but not in non-GSCs or normal neural stem cells, under a 1% O2 condition. Both HIF1? and HIF2? positively regulated CDH5 level in GSCs and could bind to the promoter of CDH5. Furthermore, CDH5 contributed to the vasculogenic mimicry of GSCs, especially under hypoxic conditions. CONCLUSIONS: The specific expression of CDH5 in GSCs may contribute to GSC-derived neovasculogenesis in glioblastoma multiforme, especially under hypoxic conditions, revealing novel tumorigenic mechanisms contributed by GSCs.

Author(s): 
Mao, Xing-Gang
Xue, Xiao-Yan
Wang, Liang
Zhang, Xiang
Yan, Ming
Tu, Yan-yang
Lin, Wei
Jiang, Xiao-Fan
Ren, Hong-Gang
Zhang, Wei
Song, Shao-Jun
Item Type: 
Journal Article
Publication Title: 
Neuro-Oncology
Journal Abbreviation: 
Neuro-oncology
Publication Date: 
7/13/2015
Publication Year: 
2013
Pages: 
865-879
Volume: 
15
Issue: 
7
ISSN: 
1523-5866
DOI: 
10.1093/neuonc/not029
Library Catalog: 
PubMed
Extra: 
PMID: 23645533 PMCID: PMC3688011

Turabian/Chicago Citation

Xing-Gang Mao, Xiao-Yan Xue, Liang Wang, Xiang Zhang, Ming Yan, Yan-yang Tu, Wei Lin, Xiao-Fan Jiang, Hong-Gang Ren, Wei Zhang and Shao-Jun Song. 7/13/2015. "CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia." Neuro-Oncology 15: 7: 865-879. 10.1093/neuonc/not029.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/neuonc/not029 | issn = 1523-5866 | volume = 15 | pages = 865-879 | last = Mao | first = Xing-Gang | coauthors = Xue, Xiao-Yan, Wang, Liang, Zhang, Xiang, Yan, Ming, Tu, Yan-yang, Lin, Wei, Jiang, Xiao-Fan, Ren, Hong-Gang, Zhang, Wei, Song, Shao-Jun | title = CDH5 is specifically activated in glioblastoma stemlike cells and contributes to vasculogenic mimicry induced by hypoxia | journal = Neuro-Oncology | date = 7/13/2015 | pmid = | pmc = }} </ref>