VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression
VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression
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DOI：
10.1016/j.cyto.2011.03.008
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发表时间：
2011-07-01
期刊：
影响因子：
3.8
通讯作者：
Zhang, Shuyu
中科院分区：
文献类型：
--
作者：
Liu, Pengfei;Zhou, Jundong;Zhang, Shuyu
血管内皮生长因子C（VEGF-C）是血管生成和淋巴管生成的关键调节因子。VEGF-C也与食管癌的发展有关。采用实时荧光定量PCR方法检测38例食管鳞癌组织及相应癌旁正常食管组织中VEGF-C及其受体mRNA的表达水平。VEGF-C、VEGFR-2和VEGFR-3的mRNA水平在ESCC中比相应侧正常组织显著上调。为了探讨VEGF-C对食管癌进展的影响，在食管癌细胞系TE-1和Eca-109中操纵VEGF-C的表达。VEGF-C转录、翻译和分泌在用VEGF-C过表达载体稳定转染的细胞中显著增强，或在VEGF-C shRNA转染的细胞系中减弱。在体外，TE-1细胞稳定转染VEGF-C过表达载体表现出细胞增殖，迁移和病灶形成的速度增加，而敲低VEGF-C抑制细胞增殖，迁移和病灶形成。对Eca-109细胞获得了类似的结果。VEGF-C通过转录CNTN-1介导生物学功能，CNTN-1与肿瘤侵袭和转移有关。VEGF-C的表达与CNTN-1的表达相关，CNTN-1的沉默可逆转VEGF-C诱导的细胞增殖和迁移。此外，接种VEGF-C shRNA转染细胞的裸鼠通过减少VEGFR-2和VEGFR-3磷酸化和微血管形成而表现出体内肿瘤大小显著减小。VEGF-C上调可能参与食管肿瘤的进展。以VEGF-C为靶点的RNA干扰（RNAi）是一种潜在的食管癌治疗方法。(C)2011爱思唯尔有限公司保留所有权利。
Vascular endothelial growth factor C (VEGF-C) is a key regulator of angiogenesis and lymphangiogenesis. VEGF-C is also implicated in the development of esophageal cancer. We investigated the mRNA levels of VEGF-C and its receptors in 38 esophageal squamous cell carcinoma specimens (ESCCs) and matched adjacent normal esophageal tissues via real-time PCR. The mRNA levels of VEGF-C, VEGFR-2 and VEGFR-3 were significantly upregulated in ESCCs versus respective side normal tissues. To explore the influence of VEGF-C on esophageal cancer progression, the expression of VEGF-C was manipulated in esophageal cancer cell lines TE-1 and Eca-109. VEGF-C transcription, translation and secretion were significantly enhanced in cells stably transfected with a VEGF-C overexpression vector or attenuated in VEGF-C shRNA-transfected cell lines. In vitro, TE-1 cells stably transfected with a VEGF-C overexpression vector exhibited an increased rate of cell proliferation, migration and focus formation, whereas knockdown of VEGF-C inhibited cell proliferation, migration and focus formation. Similar results were obtained for Eca-109 cells. VEGF-C mediated biological function through transcription of CNTN-1, which is implicated in tumor invasion and metastasis. The expression of VEGF-C was correlated with that of CNTN-1 and cell proliferation and migration induced by VEGF-C were reversed by silencing of CNTN-1. In addition, nude mice inoculated with VEGF-C shRNA-transfected cells exhibited a significantly decreased tumor size in vivo via reduced VEGFR-2 and VEGFR-3 phosphorylation and microvessel formation. VEGF-C upregulation may be involved in esophageal tumor progression. Vector-based RNA interference (RNAi) targeting VEGF-C is a potential therapeutic method for human esophageal carcinoma. (C) 2011 Elsevier Ltd. All rights reserved.