Angiogenesis in Gliomas: Biology and Molecular Pathophysiology
Angiogenesis in Gliomas: Biology and Molecular Pathophysiology
复制标题
DOI：
10.1111/j.1750-3639.2005.tb00115.x
复制
发表时间：
2005-10
期刊：
影响因子：
6.4
通讯作者：
I. Fischer;J. Gagner;M. Law;E. Newcomb;D. Zagzag
中科院分区：
文献类型：
--
作者：
I. Fischer;J. Gagner;M. Law;E. Newcomb;D. Zagzag
多形性胶质母细胞瘤（GBM）的特征是旺盛的血管生成，这是肿瘤生长和进展的关键事件。导致这种变化的病理机制和胶质瘤的生物学行为仍不清楚。一种机制可能涉及胶质瘤细胞对天然血管的共选择诱导内皮细胞表达血管生成素-2。随后，血管凋亡和退化导致坏死和缺氧。这反过来诱导血管生成，这与周围坏死的假扁平胶质瘤细胞中缺氧诱导因子（HIF）-1 α和血管内皮生长因子（VEGF）的表达相关。在这里，我们回顾了HIF-1依赖性和HIF-1非依赖性胶质瘤相关血管生成的分子和细胞机制。在GBM中，肿瘤缺氧和遗传改变通常同时发生，并共同诱导HIF-1的表达。肿瘤对HIF-1的血管生成反应由HIF-1调节的靶基因介导，导致几种促血管生成因子如VEGF和其他适应性反应分子的上调。了解这些调节过程在肿瘤新生血管形成、肿瘤生长和进展以及对治疗的抵抗中的作用，将最终导致GBM的改进的抗血管生成疗法的发展。
Glioblastoma multiforme (GBM) is characterized by exuberant angiogenesis, a key event in tumor growth and progression. The pathologic mechanisms driving this change and the biological behavior of gliomas remain unclear. One mechanism may involve cooption of native blood vessels by glioma cells inducing expression of angio‐poietin‐2 by endothelial cells. Subsequently, vascular apoptosis and involution leads to necrosis and hypoxia. This in turn induces angiogenesis that is associated with expression of hypoxia‐inducible factor (HIF)‐1 a and vascular endothelial growth factor (VEGF) in perinecrotic pseudopalisading glioma cells. Here we review the molecular and cellular mechanisms implicated in HIF‐1 ‐dependent and HIF‐1 ‐independent glioma‐associated angiogenesis. In GBMs, both tumor hypoxia and genetic alterations commonly occur and act together to induce the expression of HIF‐1. The angiogenic response of the tumor to HIF‐1 is mediated by HIF‐1‐regulated target genes leading to the upregulation of several proangiogenic factors such as VEGF and other adaptive response molecules. Understanding the roles of these regulatory processes in tumor neovascularization, tumor growth and progression, and resistance to therapy will ultimately lead to the development of improved antiangiogenic therapies for GBMs.