Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α
Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α
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DOI：
10.3892/or.2014.3454
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发表时间：
2014-11-01
期刊：
影响因子：
4.2
通讯作者：
Huang, Shuyun
中科院分区：
文献类型：
--
作者：
Huang, Min;Ke, Yiquan;Huang, Shuyun
哺乳动物雷帕霉素靶蛋白（mTOR）是恶性胶质瘤的重要调控因子。血管生成模拟（VM）描述了由高度恶性肿瘤细胞建立的不同于内皮血管的功能通道。我们前期的研究证实了VM在成神经管细胞瘤和胶质母细胞瘤中的存在及其临床意义。本研究通过免疫组织化学和CD34/PAS组织化学双染色，在127例胶质瘤中鉴定出34例VM结构（26.8%），这些VM结构与胶质瘤标本中mTOR的表达相关。体外3D培养U87恶性胶质母细胞瘤细胞在Matrigel上形成类似HUVECs的管状结构，mtor特异性抑制剂雷帕霉素在常氧和缺氧条件下均能抑制U87恶性胶质母细胞瘤细胞VM的形成。此外，雷帕霉素和mTOR siRNA抑制了VM形成信号级联中的分子，特别是HIF-1 α。综上所述，我们的研究结果表明mTOR信号参与了VM的形成，并且可能是胶质瘤的潜在治疗靶点。
The mammalian target of rapamycin (mTOR) is a crucial regulator in malignant gliomas. Vasculogenic mimicry (VM) describes functional channels established by highly malignant tumor cells that is different from endothelium-lined blood vessels. Our previous studies confirmed the existence and clinical significance of VM in medulloblastoma and glioblastoma. In the present study, by immunohistochemical and CD34/PAS histochemical double-staining, 34 cases (26.8%) with VM structures were identified among a total of 127 glioma cases, and these VM structures were associated with mTOR expression in the glioma specimens. In vitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. In addition, rapamycin and mTOR siRNA inhibited molecules in the signaling cascade of VM formation, particularly HIF-1 alpha. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas.