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

越来越多的证据表明，干细胞中的自我更新调节因子Oct-3/4的表达水平与各种实体肿瘤的进展呈正相关。然而，关于Oct-3/4在胶质母细胞瘤中对肿瘤血管生成的影响却知之甚少。在本研究中，我们将U251/EGFP-Oct-3/4细胞移植到裸鼠体内，以评价Oct-3/4在肿瘤血管生成中的作用。肿瘤大小和肿瘤内生长的大血管数量均明显增加。在体外血管生成模型中，U251/EGFP-OCT-3/4细胞的条件培养液显著促进了毛细血管样管的形成。在U251/EGFP-Oct-3/4细胞中，在HIF1a调控下，VEGFmRNA表达上调，HIF1a蛋白表达增强，核转位增加。我们的结果表明，表达Oct-3/4的胶质瘤细胞能够通过促进肿瘤血管生成来适应肿瘤的低氧环境。

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.