CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells
CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells
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DOI：
10.1016/j.canlet.2014.11.015
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发表时间：
2015-02-28
期刊：
影响因子：
9.7
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
--
作者：
Liu, Guan-Ting;Huang, Yuan-Li;Tang, Chih-Hsin
软骨肉瘤是一种原发性恶性骨癌，具有很强的局部侵袭能力并引起远处转移。血管生成是肿瘤生长和转移的关键步骤。趋化因子 CCL5（以前称为 RANTES）已被证明可以促进肿瘤进展和转移。然而，CCL5 与人软骨肉瘤中血管内皮生长因子 (VEGF) 表达和血管生成的关系大多未知。在本研究中，CCL5 增加 VEGF 表达，并在体外促进软骨肉瘤介质介导的血管生成，以及在体内鸡绒毛尿囊膜和基质胶塞裸鼠模型中的血管生成作用。在 CCL5 处理的软骨肉瘤细胞与对照细胞中进行 MicroRNA 分析，以研究 CCL5 介导的促进软骨肉瘤血管生成的机制。在受CCL5调节的miRNA中，miR-199a是CCL5处理后下调最多的miRNA。此外，与miR-199a模拟物共转染在体外和体内逆转了CCL5介导的VEGF表达和血管生成。此外，在异种移植肿瘤血管生成模型中，CCL5 的过表达通过下调 miR-199a 来增加肿瘤相关血管生成和肿瘤生长。综上所述，这些结果表明 CCL5 通过下调 miR-199a 促进人软骨肉瘤细胞中 VEGF 依赖性血管生成。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been shown to facilitate tumor progression and metastasis. However, the relationship of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. MicroRNA analysis was performed in CCL5-treated chondrosarcoma cells versus control cells to investigate the mechanism of CCL5-mediated promotion of chondrosarcoma angiogenesis. Among the miRNAs regulated by CCL5, miR-199a was the most downregulated miRNA after CCL5 treatment. In addition, co-transfection with miR-199a mimic reversed the CCL5-mediated VEGF expression and angiogenesis in vitro and in vivo. Moreover, overexpression of CCL5 increased tumor-associated angiogenesis and tumor growth by downregulating miR-199a in the xenograft tumor angiogenesis model. Taken together, these results demonstrated that CCL5 promotes VEGF-dependent angiogenesis in human chondrosarcoma cells by downregulating miR-199a. (C) 2014 Elsevier Ireland Ltd. All rights reserved.