Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors.
Soluble VEGFR-2: an antilymphangiogenic variant of VEGF receptors.
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DOI：
10.1111/j.1749-6632.2010.05714.x
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发表时间：
2010-10
影响因子：
5.2
通讯作者：
Ambati J
中科院分区：
文献类型：
--
作者：
Pavlakovic H;Becker J;Albuquerque R;Wilting J;Ambati J
血管内皮生长因子(VEGF)家族的分泌蛋白及其受体是血管发育(血管生成)和淋巴管发育(淋巴管生成)的主要调节因子。血管内皮生长因子通过一个复杂的受体酪氨酸激酶系统发挥作用，该系统可以是膜结合的，也可以是可溶的。有关受体系统的新数据仍在不断涌现，从而增加了该系统的复杂性。最近，人们发现了VEGFR-2的一种可溶性形式，称为sVEGFR-2，它是选择性剪接的结果。早些时候已经表明，一种分泌/可溶形式的VEGFR-1，称为sVEGFR-1，通过选择性剪接产生，并通过结合VEGF-A发挥抗血管生成的作用。新发现的sVEGFR-2剪接变异体结合淋巴管生长因子VEGFR-C，从而抑制VEGFR-3的激活，从而抑制淋巴管内皮细胞的增殖。在小鼠胚胎中，它的失活允许皮肤淋巴管的增殖和淋巴管进入角膜。肿瘤淋巴管生成似乎影响了恶性细胞的转移行为。已经发现sVEGFR-2的下调与神经母细胞瘤的恶性进展有关，神经母细胞瘤的特征是进展期的淋巴源性转移。数据表明，淋巴管生成同时受激活剂和抑制物的调节，其平衡对健康和疾病至关重要。
The Vascular Endothelial Growth Factor (VEGF) family of secreted proteins and their receptors are major regulators of blood vessel development (hemangiogenesis) and lymphatic vessel development (lymphangiogenesis). VEGF acts through a complex system of receptor tyrosine kinases, which can be membrane-bound or soluble. New data concerning the receptor system are still emerging, thus contributing to the complexity of the system. Very recently a soluble form of VEGFR-2, termed sVEGFR-2, that is a result of alternative splicing has been discovered. It has been shown earlier that a secreted/soluble form of VEGFR-1, termed sVEGFR-1, is produced by alternative splicing and exerts an anti-hemangiogenic effect by binding VEGF-A. The newly discovered spliced variant of sVEGFR-2 binds the lymphangiogenic growth factor VEGF-C and thus inhibits VEGF-C-induced activation of VEGFR-3, consequently inhibiting lymphatic endothelial cell proliferation. Its inactivation in murine embryos permits hyperplasia of dermal lymphatics and invasion of lymphatics into the cornea. Tumor lymphangiogenesis seems to influence the metastatic behavior of malignant cells. A correlation has been found between the downregulation of sVEGFR-2 and the malignant progression of neuroblastoma, which is characterized e.g. by lymphogenic metastases in progressed stages. Data show that lymphangiogenesis is regulated by both activators and inhibitors, and its balance is crucial in health and disease.
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