The soluble fragment of VE-cadherin inhibits angiogenesis by reducing endothelial cell proliferation and tube capillary formation
The soluble fragment of VE-cadherin inhibits angiogenesis by reducing endothelial cell proliferation and tube capillary formation
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DOI：
10.1038/cgt.2010.26
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发表时间：
2010-10-01
影响因子：
6.4
通讯作者：
Lu, H.
中科院分区：
文献类型：
--
作者：
Li, H.;Shi, X.;Lu, H.
血管内皮特异性钙粘蛋白（VE-cadherin）是一种内皮细胞特异性粘附分子，定位于细胞-细胞接触部位。它参与生理性和病理性血管生成。本研究表明，在体外实验中，与cadherin 1-3外结构域对应的VE-cadherin （EC1-3）可溶性n端片段抑制了血管内皮生长因子刺激的基质模型内皮细胞增殖和毛细血管结构的形成。在体内，EC1-3在小鼠结肠癌模型中进行了测试。将表达ec1 -3的结肠癌C51细胞皮下移植到裸鼠体内，观察肿瘤生长和血管生成情况。在第33天，肿瘤的平均体积减小（510 +/- 104 mm，对照组为990 +/- 120 mm）。同样，将EC1-3产病毒细胞注射到已建立的C51肿瘤中，可抑制33%的肿瘤生长。肿瘤切片血管的免疫组织学染色显示肿瘤内血管生成明显减少。EC1-3未引起小鼠肺、肝、脾、心、脑血管损伤。以上结果表明，VE-cadherin EC1-3的可溶性n端片段可能通过靶向肿瘤血管生成发挥抗肿瘤作用，包括阻断内皮细胞增殖和毛细血管形成，对正常器官无明显毒性。癌症基因治疗（2010）17,700-707；doi: 10.1038 / cgt.2010.26;2010年6月18日在线发布
Vascular endothelial-specific cadherin (VE-cadherin) is an endothelial cell-specific adhesion molecule, localized at cell-cell contact sites. It is involved in physiological and pathological angiogenesis. In this study, we showed that in vitro a soluble N-terminal fragment of VE-cadherin (EC1-3) corresponding to cadherin 1-3 ectodomains inhibited vascular endothelial growth factor-stimulated endothelial cell proliferation and capillary tube structure formation in the matrigel model. In vivo, EC1-3 was tested in a murine colon cancer model. EC1-3-expressing colon cancer C51 cells were subcutaneously grafted into nude mice, and tumor growth and angiogenesis were evaluated. At day 33, the mean volume of the tumors developed was reduced (510 +/- 104 versus 990 +/- 120 mm(3) for control). Similarly, injection of EC1-3 virus-producing cells into established C51 tumors resulted in an inhibition by 33% of tumor growth. Immunohistological staining of vessels on tumor sections showed a significantly reduced intratumoral angiogenesis. Furthermore, EC1-3 did not induce vessel injury in the lung, liver, spleen, heart and brain in the mice. These results suggest that the soluble N-terminal fragment of VE-cadherin EC1-3 could exert an antitumoral effect by targeting tumor angiogenesis, which included blocking endothelial cell proliferation and capillary tube formation with no obvious toxicity on normal organs. Cancer Gene Therapy (2010) 17, 700-707; doi:10.1038/cgt.2010.26; published online 18 June 2010