title: VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression.
abstract: 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.
authors.affiliation: Department of Gastroenterology, The Affiliated Jiangyin Hospital of Southeast University, Jiangyin 214400, China. jylpf@163.com
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Xie
authors.forename: Fangjun
authors.initials: F
authors.lastname: Wang
authors.forename: Bingtuan
authors.initials: B
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Shen
authors.forename: Wu
authors.initials: W
authors.lastname: Ye
authors.forename: Bin
authors.initials: B
authors.lastname: Xiang
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Zhu
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058967:Contactin 1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D051379:Mice; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C548669:CNTN1 protein, human; D058967:Contactin 1; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3