Sakuma Takahiro, Nakagawa Takao, Ido Kazunori, Takeuchi Hiroaki, Sato Kazufumi, Kubota Toshihiko
Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193, Japan.
J Neurooncol. 2008 Jun;88(2):143-55. doi: 10.1007/s11060-008-9559-8.
We studied the expression of vascular endothelial growth factor-A (VEGF-A) and mRNA stability factor HuR in 40 supratentorial meningiomas using RT-PCR, ELISA and immunohistochemistry, and analyzed their associations with the clinicopathological characteristics, including microvascular density (MVD), peritumoral brain edema (PTBE), histological subtypes and grades, and the performance of preoperative arterial embolization. Furthermore, we investigated the involvement of HuR in the upregulation of VEGF-A expression using primary meningioma cell cultures. The level of VEGF-A is elevated in meningiomas with PTBE and in higher grade meningiomas. Preoperative arterial embolization did not significantly increase the level of VEGF-A, but it did increase the expression of HuR in tumor tissues. HuR expression was correlated positively with VEGF-A expression in meningioma tissues. In in vitro experiments, hypoxia induced the upregulation of VEGF-A expression and the cytoplasmic translocation of HuR protein in meningioma cells, and inhibition of the cytoplasmic translocation of HuR reduced the upregulation of VEGF-A expression in meningioma cells. These findings suggest that the expression of VEGF-A relates to the development of PTBE with meningiomas and the histological grade, and that HuR is involved in the upregulation of VEGF-A expression in human meningiomas.
我们运用逆转录聚合酶链反应(RT-PCR)、酶联免疫吸附测定(ELISA)和免疫组织化学方法,研究了40例幕上脑膜瘤中血管内皮生长因子A(VEGF-A)和mRNA稳定因子HuR的表达情况,并分析了它们与临床病理特征的相关性,这些特征包括微血管密度(MVD)、瘤周脑水肿(PTBE)、组织学亚型和分级,以及术前动脉栓塞的效果。此外,我们利用原代脑膜瘤细胞培养研究了HuR在VEGF-A表达上调中的作用。PTBE脑膜瘤和高级别脑膜瘤中VEGF-A水平升高。术前动脉栓塞并未显著提高VEGF-A水平,但确实增加了肿瘤组织中HuR的表达。在脑膜瘤组织中,HuR表达与VEGF-A表达呈正相关。在体外实验中,缺氧诱导脑膜瘤细胞中VEGF-A表达上调和HuR蛋白的胞质转位,抑制HuR的胞质转位可降低脑膜瘤细胞中VEGF-A表达的上调。这些发现表明,VEGF-A的表达与脑膜瘤伴发PTBE的发生及组织学分级有关,且HuR参与了人脑膜瘤中VEGF-A表达的上调。