VEGF as a key mediator of angiogenesis in cancer
VEGF as a key mediator of angiogenesis in cancer
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DOI：
10.1159/000088478
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Carmeliet, P
中科院分区：
文献类型：
--
作者：
Carmeliet, P
血管内皮生长因子(VEGF)是一种分子量约为45 kDa的同源二聚体糖蛋白。它是血管生成(新血管形成)的关键介质，与血管内皮细胞上表达的两个血管内皮生长因子受体(血管内皮生长因子受体-1和血管内皮生长因子受体-2)结合。在健康的人类中，血管内皮生长因子促进胚胎发育中的血管生成，并在成年人的伤口愈合中发挥重要作用。血管内皮生长因子是肿瘤血管生成的关键介质，其表达受癌基因表达、多种生长因子和缺氧的上调。血管生成对癌症的发展和生长是必不可少的：在肿瘤生长超过1-2毫米之前，它需要血管提供营养和氧气。肿瘤产生血管内皮生长因子和其他生长因子，形成“血管生成开关”，在肿瘤内部和周围形成新的血管，使其呈指数级增长。在血管内皮生长因子的影响下形成的肿瘤血管在结构和功能上都是异常的。血管形状不规则，曲折，有死端，没有组织成小静脉、小动脉和毛细血管。它们也是渗漏和出血的，这会导致高间质压力。这些特征意味着肿瘤的血流是次优的，导致缺氧和进一步的血管内皮生长因子的产生。血管内皮生长因子在肿瘤血管生成中的中心作用使其成为抗癌治疗的合理靶点。版权所有(C)2005 S.Karger AG，巴塞尔。
Vascular endothelial growth factor (VEGF) is a homodimeric glycoprotein with a molecular weight of approximately 45 kDa. It is the key mediator of angiogenesis (the formation of new blood vessels), and binds two VEGF receptors (VEGF receptor-1 and VEGF receptor-2), which are expressed on vascular endothelial cells. In healthy humans, VEGF promotes angiogenesis in embryonic development and is important in wound healing in adults. VEGF is the key mediator of angiogenesis in cancer, in which it is up-regulated by oncogene expression, a variety of growth factors and also hypoxia. Angiogenesis is essential for cancer development and growth: before a tumor can grow beyond 1-2 mm, it requires blood vessels for nutrients and oxygen. The production of VEGF and other growth factors by the tumor results in the 'angiogenic switch', where new vasculature is formed in and around the tumor, allowing it to grow exponentially. Tumor vasculature formed under the influence of VEGF is structurally and functionally abnormal. Blood vessels are irregularly shaped, tortuous, have dead ends and are not organized into venules, arterioles and capillaries. They are also leaky and hemorrhagic, which leads to high interstitial pressure. These characteristics mean that tumor blood flow is suboptimal, resulting in hypoxia and further VEGF production. This central role of VEGF in the production of tumor vasculature makes it a rational target for anticancer therapy. Copyright (C) 2005 S. Karger AG, Basel.