Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and-2
Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and-2
复制标题
DOI：
10.1101/cshperspect.a006627
复制
发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Lawler, Jack
中科院分区：
文献类型：
--
作者：
Lawler, Patrick R.;Lawler, Jack
血小板反应蛋白 TSP-1 和 TSP-2 是血管生成的有效内源性抑制剂。它们通过直接影响内皮细胞迁移、增殖、存活和凋亡以及拮抗 VEGF 活性来抑制血管生成。介导 TSP-1 和 TSP-2 作用的几种膜受体系统和信号转导分子已被阐明。 TSP-1 和 TSP-2 通过 CD36、CD47 和整合素发挥直接作用。最近的数据表明 CD36 和 β1 整合素协同传递由 TSP-1 和 TSP-2 启动的信号。此外，这些受体似乎与 VEGFR2 结合，形成整合血管生成的正负信号的平台。促血管生成信号转导通路和抗血管生成信号转导通路之间的串扰可能使 TSP-1 和 TSP-2 通过拮抗存活通路同时激活凋亡通路来抑制血管生成。 CD36 和 CD47 均参与一氧化氮 (NO) 的抑制。对 TSP 对血管生成的分子调节的理解的进展为癌症实验治疗的创新铺平了道路，并且可能继续为其他疾病过程的发现提供广阔的途径。
Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF. Several of the membrane receptor systems and signal transduction molecules that mediate the effects of TSP-1 and TSP-2 have been elucidated. TSP-1 and TSP-2 exert their direct effects through CD36, CD47, and integrins. Recent data indicate that CD36 and beta 1 integrins collaborate to transmit the signals that are initiated by TSP-1 and TSP-2. Furthermore, these receptors appear to associate with VEGFR2 to form a platform for the integration of positive and negative signals for angiogenesis. Cross talk between pro- and antiangiogenic signal transduction pathways may enable TSP-1 and TSP-2 to inhibit angiogenesis byantagonizing survival pathways while also activating apoptotic pathways. CD36 and CD47 are both involved in the suppression of nitric oxide (NO). Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.