Endothelial receptor tyrosine kinases involved in angiogenesis.
Endothelial receptor tyrosine kinases involved in angiogenesis.
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DOI：
10.1083/jcb.129.4.895
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发表时间：
1995-05
期刊：
影响因子：
--
通讯作者：
Alitalo K
中科院分区：
文献类型：
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作者：
Mustonen T;Alitalo K
即时生长、成体组织的重塑和再生以及实体瘤生长只能伴随血管形成而发生。成血管细胞和造血前体细胞从中胚层分化，形成卵黄囊的血岛和胚胎的初级血管系统（血管发生）。血管树的其余部分的形成被认为是由于血管从预先存在的血管发芽而发生的，这一过程称为血管生成（9）。内皮细胞可以产生几种类型的功能和形态上不同的血管。在血管生成刺激下，内皮细胞可以重新进入细胞周期，降解下面的基底膜并迁移，形成伸入血管周围基质的毛细血管芽，并再次退出细胞周期，随后分化形成功能上适应其组织环境的新血管。因此，与组织发育和再生同时发生的血管生成取决于内皮细胞增殖、迁移、分化和存活的严格控制过程。另一方面，内皮细胞调节系统的功能障碍是许多疾病的关键特征。最重要的是，肿瘤生长和转移已被证明是血管生成依赖性的（9）。调节细胞生长和分化的关键信号由多肽生长因子及其跨膜受体介导，其中许多是酪氨酸激酶。已经表征了几个受体酪氨酸激酶家族（46）。目前已知的主要的转导血管生成刺激的生长因子和受体示意性地显示在图1中。它们中的一些，如成纤维细胞生长因子受体（FGFR）、血小板衍生生长因子-BB（PDGFRB）、转化生长因子-ol（表皮生长因子受体，EGFR）和肝细胞生长因子（Met癌蛋白）在许多组织和细胞类型中广泛表达，而其他则是严格的内皮细胞特异性（46）。FGF（综述见参考文献1）已显示对培养的内皮细胞具有促有丝分裂和趋化作用。FGF还刺激蛋白酶如col-1的产生。
EVELOPMENTAL growth, the remodeling and regeneration of adult tissues as well as solid tumor growth, can only occur accompanied by blood vessel formation. Angioblasts and hemopoietic precursor cells differentiate from the mesoderm and form the blood islands of the yolk sac and the primary vascular system of the embryo (vasculogenesis). The formation of the rest of the vascular tree is thought to occur as a result of vascular sprouting from pre-existing vessels, a process called angiogenesis (9). Endothelial cells can give rise to several types of functionally and morphologically distinct vessels. Upon angiogenic stimuli, endothelial ceils can re-enter the cell cycle, degrade the underlying basement membrane and migrate, forming capillary sprouts that projectinto theperivascular stroma, and again withdraw from the cell cycle and subsequently differentiate to form new vessels that are functionally adapted to their tissue environment. Thus, angiogenesis, concurrent with tissue development and regeneration depends on the tightly controlled processes of endothelial cell proliferation, migration, differentiation, and survival. On the other hand, dysfunction of the endothelial cell regulatory system is a key feature of many diseases. Most importantly, tumor growth and metastasis have been shown to be angiogenesis dependent (9). Key signals regulating cell growth and differentiation are mediated by polypeptide growth factors and their transmembrane receptors, many of which are tyrosine kinases. Several families of receptor tyrosine kinases have been characterized (46). The main currently known growth factors and receptors transducing angiogenic stimuli are schematically shown in Fig. 1. Some of them, such as the receptors for fibroblast growth factors (FGFR), 1 platelet-derived growth factor-BB (PDGFRB), transforming growth factor-ol (epidermal growth factor receptor, EGFR), and hepatocyte growth factor (Met oncoprotein) are widely expressed in many tissues and cell types, whereas others are strictly endothelial cell specific (46). FGFs (for a review see reference 1) have been shown to be mitogenic and chemotactic for cultured endothelial cells. FGFs also stimulate the production of proteases such as col-