Oct-3/4 promotes tumor angiogenesis through VEGF production in glioblastoma

Oct-3/4 通过胶质母细胞瘤中 VEGF 的产生促进肿瘤血管生成

• 批准号: 23592129
• 负责人: HISAAKI Takahashi
• 金额: $ 3.33万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592129/
• 关键词: 膠芽腫; Oct-3/4; 血管新生; VEGF; HIF1; AKT; グリオブラストーマ; 腫瘍幹細胞; 浸潤

Accumulating evidence shows that the expression level of Oct-3/4, a self-renewal regulator in stem cells, is positively correlated with the progression of various solid tumors. However, little is known regarding the influence of Oct-3/4 in the tumor angiogenesis of glioblastoma. In this study, we subcutaneously transplanted U251/EGFP-Oct-3/4 cells into nude mice to evaluate the roles of Oct-3/4 in the tumor angiogenesis. Both tumor size and the number of large vessels growing in the tumor were markedly increased. In an in vitro model of angiogenesis, conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation. In U251/EGFP-Oct-3/4 cells, VEGF mRNA was upregulated under the control of HIF1a, and enhanced protein expression and nuclear translocation of HIF1a were observed. Our results demonstrate that Oct-3/4-expressing glioma cells have the ability to adapt to low-oxygen environments of tumor by promoting tumor angiogenesis.

越来越多的证据表明，干细胞自我更新调节因子Oct-3/4的表达水平与各种实体瘤的进展呈正相关。然而，关于Oct-3/4在胶质母细胞瘤的肿瘤血管生成中的影响知之甚少。本研究通过将U251/EGFP-Oct-3/4细胞移植于裸鼠皮下，观察Oct-3/4在肿瘤血管生成中的作用。肿瘤大小和肿瘤中生长的大血管数量均显著增加。在血管生成的体外模型中，来自U251/EGFP-Oct-3/4细胞的条件培养基显著加速毛细血管样管的形成。在U251/EGFP-Oct-3/4细胞中，VEGF mRNA在HIF 1a的调控下表达上调，HIF 1a蛋白表达增强，并出现核转位。我们的研究结果表明，Oct-3/4表达胶质瘤细胞具有通过促进肿瘤血管生成来适应肿瘤低氧环境的能力。