Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis
Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis
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DOI：
10.1016/j.bbrc.2008.04.168
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发表时间：
2008-07-11
影响因子：
3.1
通讯作者：
Lee, Seung-Taek
中科院分区：
文献类型：
--
作者：
Shin, Won-Sik;Maeng, Yong-Sun;Lee, Seung-Taek
人PTK 7是一种有缺陷的受体蛋白酪氨酸激酶，其表达在包括结肠直肠癌在内的各种癌症中上调。为了确定PTK 7是否在血管生成中起作用，我们表达并纯化了PTK 7的胞外结构域（可溶性PTK 7; sPTK 7）作为诱饵受体以抵消内源性PTK 7的作用。人脐血管内皮细胞（HUVECs）的毛细血管样管形成伴随着PTK 7 mRNA水平的调节。用sPTK 7中和内源性PTK 7以剂量依赖性方式抑制血管内皮生长因子（VEGF）诱导的HUVECs的管形成、迁移和侵袭。sPTK 7减少VEGF诱导的粘着斑激酶（FAK）和桩蛋白的磷酸化、桩蛋白向粘着斑的再定位以及应力纤维的形成。此外，在体内，sPTK 7抑制VEGF诱导的血管生成。使用siRNA敲低PTK 7也抑制VEGF诱导的管形成，支持sPTK 7特异性阻断内源性PTK 7的功能。这些结果表明，PTK 7不仅在内皮细胞的管形成、迁移和侵袭中起重要作用，而且在血管生成中起重要作用。(c)2008年爱思唯尔公司All rights reserved.
Human PTK7 is a defective receptor protein tyrosine kinase and its expression is upregulated in various cancers including colorectal carcinomas. To determine whether PTK7 functions in angiogenesis, we have expressed and purified the extracellular domain of PTK7 (soluble PTK7; sPTK7) as a decoy receptor to counteract the effects of endogenous PTK7. Capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs) was accompanied by modulation in the PTK7 mRNA level. Neutralization of endogenous PTK7 with sPTK7 inhibited vascular endothelial growth factor (VEGF)-induced tube formation, migration, and invasion of HUVECs in a dose-dependent manner. sPTK7 reduced VEGF-induced phosphorylation of focal adhesion kinase (FAK) and paxillin, relocalization of paxillin to focal adhesions, and formation of stress fibers. Moreover, sPTK7 inhibited VEGF-incluced angiogenesis in vivo. Knockdown of PTK7 using siRNA also inhibited VEGF-induced tube formation, supporting that sPTK7 specifically blocks function of the endogenous PTK7. These results demonstrate that PTK7 plays an important role not only in tube formation, migration, and invasion of endothelial cells but also in angiogenesis. (c) 2008 Elsevier Inc. All rights reserved.