VEGF在肿瘤生长和血管生成中的作用

Role of the vascular endothelial growth factor signaling pathway in tumor growth and angiogenesis

新血管的形成(angiogenesis)是肿瘤生长转移和传播过程中的一种基本活动.因此,在癌症研究领域,人们对研究肿瘤血管生成的分子机制十分感兴趣.血管内皮生长因子(vascular endothelial growth factor,VEGF)路径是这一过程的关键调节者.VEGF/VEGFR轴由多重配基和受体质量叠加交错组成,并且受体与配基结合具有专一性,在不同的细胞中具有不同的细胞类型表达和功能.启动VEGFR信号通路,触发了一个网状的信号过程,从而促进血管内皮细胞生长、转移和存活.此外,VEGF介导的血管渗透性,已经被证实与恶性渗出有关.最近,VEGF的一个重要作用表现为可动员内皮祖细胞从骨髓向远处转移从而形成新生血管.VEGF促进肿瘤血管生成的作用和与人类癌症的发病机制的关系是确定的,因而有必要设计和发展针对这一途径的抑制因子.许多的抗VEGF/VEGFR治疗的研究表明,这些因子能有效地抑制临床前模型的血管生成和肿瘤生长.因此,抑制VEGF途径被确认为是一种重要的有效的抗癌模式.

New blood vessel formation（angiogenesis） is a fundamental event in the process of tumor growth and metastatic dissemination.Hence,the molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research.The vascular endothelial growth factor（VEGF） signaling pathway is well established as one of the key regulators of this process.The VEGF/ VEGF-receptor axis is composed of multiple ligands and receptors with overlapping and distinct ligand-receptor binding specificities,celltype expression,and function.Activation of the VEGF signaling pathway triggers a network of signaling processes that promote endothelial cell growth,migration,and survival from pre-existing vasculature.In addition,VEGFmediated vessel permeability has been associated with malignant effusions.More recently,an important role of VEGF has emerged in mobilization of endothelial progenitor cells from the bone marrow to distant site neovascularization.The well-established role of VEGF in promoting tumor angiogenesis and the pathogenesis of human cancers has led to the rational designand development of reagents that selectively target this pathway.Studies with various antiVEGF/VEGFR therapies have shown that these reagents can potently inhibit angiogenesis and tumor growth in preclinical models.