Zadeh Gelareh, Guha Abhijit
Arthur and Sonia Labatts Brain Tumor Center, Hospital for Sick Childrens, University of Toronto,399 Bathurst Street, Toronto, Ontario, Canada.
Front Biosci. 2003 Jan 1;8:e128-37. doi: 10.2741/964.
Since the introduction of the concept of an "angiogenic switch" driving tumor growth and malignant progression by Judah Folkman in 1971, there have been numerous scientific reports confirming the central concept that tumor growth is angiogenesis dependent. Various angiogenic genes and gene products, from both neoplastic and normal tissues, have been isolated, purified, and cloned that contribute to the 'angiogenic switch'. Of these various molecules, two have been identified that act specifically on endothelial cells. First is Vascular Endothelial Growth Factor (VEGF), the cognate receptors of which are almost specifically expressed on endothelial cells. VEGF plays a crucial role in the development of the embryonic vasculature by providing differentiation and mitogenic signals to endothelial cells and their mesodermal precursors. Second are the Angiopoietins and their cognate receptor, Tie2. Angiopoietins are primarily involved in maturation of both embryonal and adult vasculature, with Angiopoietin 1 2 being naturally occurring agonists and antagonists of Tie2 respectively, indicating a very precise level of regulation in-vivo. In this review we summarize what is known of the biological role of Angiopoietins and Tie2, their interaction with VEGF in normal and tumor related angiogenesis, with emphasis on their functional consequence in the progression and growth of malignant human astrocytomas.
自1971年朱达·福克曼提出“血管生成开关”驱动肿瘤生长和恶性进展的概念以来，已有大量科学报告证实肿瘤生长依赖血管生成这一核心概念。来自肿瘤组织和正常组织的各种血管生成基因及基因产物已被分离、纯化和克隆，它们共同促成了“血管生成开关”。在这些不同的分子中，已鉴定出两种特异性作用于内皮细胞的分子。第一种是血管内皮生长因子（VEGF），其同源受体几乎只在内皮细胞上表达。VEGF通过向内皮细胞及其中胚层前体细胞提供分化和有丝分裂信号，在胚胎血管系统发育中起关键作用。第二种是血管生成素及其同源受体Tie2。血管生成素主要参与胚胎和成人血管系统的成熟，血管生成素1和2分别是Tie2天然存在的激动剂和拮抗剂，这表明体内存在非常精确的调控水平。在这篇综述中，我们总结了血管生成素和Tie2的生物学作用、它们在正常和肿瘤相关血管生成中与VEGF的相互作用，重点阐述了它们在人类恶性星形细胞瘤进展和生长中的功能影响。
