VEGF-C contributes to head and neck squamous cell carcinoma growth and motility
VEGF-C contributes to head and neck squamous cell carcinoma growth and motility
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DOI：
10.1016/j.oraloncology.2010.02.006
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Yeudall, W. Andrew
中科院分区：
文献类型：
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作者：
Benke, Emily M.;Ji, Youngmi;Yeudall, W. Andrew
我们实验室之前的工作已经证明了趋化因子在头颈癌中的过度表达，以及在临床前模型中靶向这些蛋白质用于肿瘤治疗的实用性。然而，所涉及的机制尚未被探索。通过基因表达分析，我们发现在表达高水平CXCL5的HN12细胞中，血管内皮生长因子（VEGF-C）的表达升高。在本研究中，我们研究了VEGF-C对肿瘤细胞生长和运动的贡献。在表达高水平CXCL5的HN12细胞中，rnai介导的VEGF-C表达下调导致增殖减少。相反，在内源性CXCL5水平较低的HN4肿瘤细胞中，被迫表达VEGF-C可促进细胞生长。VEGF-C抑制HN12细胞的迁移。同样，与对照组相比，HN4细胞对从VEGF-C敲低的HN12细胞收集的条件培养基的迁移减少，而HN4/VEGF-C条件培养基刺激细胞迁移。此外，当shRNA阻断VEGF-C表达时，体内肿瘤生长明显降低。最后，在鳞状癌细胞系中VEGF-C表达的测定显示，与正常角质形成细胞相比，VEGF-C普遍过表达。这些发现支持VEGF-C在头颈部鳞状细胞癌发生中的作用。(C) 2010 Elsevier Ltd.版权所有。
Previous work from our laboratory has demonstrated overexpression of chemokines in head and neck cancer and the utility of targeting these proteins for tumor therapy in a preclinical model. However, the mechanisms involved are unexplored. Through gene expression analysis, we found that expression of vascular endothelial growth factor (VEGF-C) was elevated in HN12 cells expressing high levels of CXCL5. In the present study, we have investigated the contribution of VEGF-C to tumor cell growth and motility. RNAi-mediated knockdown of VEGF-C expression in HN12 cells, which express high levels of CXCL5, resulted in a decrease in proliferation. Conversely, forced expression of VEGF-C in HN4 tumor cells with low endogenous CXCL5 levels increased cell growth. Suppression of VEGF-C inhibited migration of HN12 cells. Similarly, HN4 cells showed reduced migration towards conditioned media collected from HN12 cells with VEGF-C knockdown compared to controls, while HN4/VEGF-C conditioned media stimulated cell migration. Moreover, tumor growth in vivo was markedly reduced when VEGF-C expression was blocked by shRNA. Finally, determination of VEGF-C expression in squamous carcinoma cell lines revealed universal overexpression compared to normal keratinocytes. These findings support a role for VEGF-C in head and neck squamous cell carcinogenesis. (C) 2010 Elsevier Ltd. All rights reserved.