最新《Cancer Cell》封面文章

　　

生物通报道，杜克大学医学院药理与癌症生物学系，外科系，病理系，Cleveland Clinic干细胞生物与再生医学系的研究者在最新的一期Cancer Cell上发表研究进展Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells。

 

文章通讯作者是杜克大学Jeremy N.Rich教授，目前任杜克大学医学院副教授。主要研究神经胶质癌症干细胞以及脑癌；β转化生长因子信号。

 

神经胶质瘤(Giiomas)亦称胶质细胞瘤简称胶质瘤，是发生于神经外胚层的肿瘤，故亦称神经外胚层肿瘤或神经上皮肿瘤肿瘤。神经胶质瘤是一种致死性癌症，它的一大特征是神经胶质癌干细胞中有血管发生。

 

由于血管的发生受低氧条件调控，研究小组对神经胶质瘤对低氧的反应进行了研究。研究发现在低氧情况下，HIF2α和多个HIF相关的基因优先在神经胶质瘤干细胞中表达，而在其他干细胞和正常神经祖细胞中没有类似现象。

 

在肿瘤样本中，HIF2α与癌症干细胞标志共同出现。体外实验证实，抑制胶质细胞癌的HIFs可有效阻止癌细胞更新、增殖和存活；而活体实验证实，抑制HIFs可减缓癌症发生的速度。对分子细胞数据进行分析发现，神经胶质瘤患者若表达HIF2A，常预后不良。

 

这些研究结果表明，神经胶质细胞瘤在低氧情况下常诱导HIF模式的病变，而且HIF2α可能成为治疗神经胶质细胞瘤的理想靶位。

（生物通 小茜）

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Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells

Zhizhong Li1,Shideng Bao2,5,Qiulian Wu2,5,Hui Wang1,Christine Eyler1,2,Sith Sathornsumetee2,Qing Shi2,Yiting Cao2,Justin Lathia2,5,Roger E. McLendon3,Anita B. Hjelmeland2,5andJeremy N. Rich1,2,4,5,,

 

1 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

2 Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA

3 Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA

4 Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA

5 Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195, USA

 

【Summary】

Glioblastomas are lethal cancers characterized by florid angiogenesis promoted in part by glioma stem cells (GSCs). Because hypoxia regulates angiogenesis, we examined hypoxic responses in GSCs. We now demonstrate that hypoxia-inducible factor HIF2 and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2 colocalizes with cancer stem cell markers. Targeting HIFs in GSCs inhibits self-renewal, proliferation, and survival invitro, and attenuates tumor initiation potential of GSCs invivo. Analysis of a molecular database reveals that HIF2A expression correlates with poor glioma patient survival. Our results demonstrate that GSCs differentially respond to hypoxia with distinct HIF induction patterns, and HIF2 might represent a promising target for antiglioblastoma therapies.