Carmeliet Peter
Center for Transgene Technology and Gene Therapy, Flander's Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium.
Oncology. 2005;69 Suppl 3:4-10. doi: 10.1159/000088478. Epub 2005 Nov 21.
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.
血管内皮生长因子（VEGF）是一种分子量约为45 kDa的同型二聚体糖蛋白。它是血管生成（新血管形成）的关键介质，可与两种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，这两种受体在血管内皮细胞上表达。在健康人体内，血管内皮生长因子在胚胎发育过程中促进血管生成，对成年人伤口愈合也很重要。血管内皮生长因子是癌症中血管生成的关键介质，在癌症中它会因癌基因表达、多种生长因子以及缺氧而上调。血管生成对癌症的发展和生长至关重要：在肿瘤生长超过1-2毫米之前，它需要血管来提供营养和氧气。肿瘤产生的血管内皮生长因子和其他生长因子会导致“血管生成开关”，肿瘤内部和周围会形成新的脉管系统，使其呈指数级生长。在血管内皮生长因子影响下形成的肿瘤脉管系统在结构和功能上都不正常。血管形状不规则、蜿蜒曲折、有盲端，且未组织成小静脉、小动脉和毛细血管。它们还具有渗漏性和出血性，这会导致高间质压力。这些特征意味着肿瘤血流不理想，导致缺氧并进一步产生血管内皮生长因子。血管内皮生长因子在肿瘤脉管系统生成中的核心作用使其成为抗癌治疗的合理靶点。
