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Objective To investigate the effects of CNTN-1 on the invasion and migration of human esophageal cancer EC9706 cells and the possible mechanism.Methods The expression of CNTN-1 in human esophageal cancer EC9706 cells was measured by qPCR and Western blot.After transfection with CNTN-1 siRNA or CNTN-1, the cells were divided into control group, scrambled siRNA group, CNTN-1 siRNA group, pcDNA3.1-vector group and pcDNA3.1-CNTN-1 group.Cell proliferation, invasion and migration were respectively analyzed by BrdU assay and Transwell test.The expression of MMP-2 and MMP-9 were detected by qPCR and Western blot.Results The mRNA and protein expression of CNTN-1 were significantly upregulated in EC9706 cells.Compared with control, cell proliferation, invasion and migration, as well as the expression of MMP-2 and MMP-9 were significantly decreased by CNTN-1 siRNA, while they were increased by CNTN-1 overexpression (P<0.05).ConclusionsCNTN-1 can influence the invasion and metastasis of esophageal cancer cells through the regulation of the expression of MMP-2 and MMP-9.
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Objective To investigate the relationship between contactin (CNTN)-1 and vascular endothelial growth factor (VEGF)-C expression levels and the recurrence,metastasis and prognosis of hepatocellular carcinoma(HCC) patients after liver transplantation.Methods Clinical data and pathological specimen of 105 patients diagnosed with primary HCC undergoing orthotopic liver transplantation were collected.The expression levels of CNTN-1 and VEGF-C in the cancerous and para-cancerous liver tissues were quantitatively measured by immunohistochemical staining.The relationship between the CNTN-1 and VEGF-C expression levels and clinicopathological characteristics,postoperative recurrence,metastasis and prognosis was statistically analyzed.Results The high expression rate of CNTN-1 and VEGF-C in liver cancerous tissues was 46.7％ and 39.0％,significantly higher compared with 11.4％ and 19.0％ in the para-cancerous tissues (both P＜0.05).Spearman correlation analysis revealed that the expression level of CNTN-1 was positively correlated with that of VEGF-C (P＜0.005).X2 test demonstrated that the expression of CNTN-1 protein was positively correlated with the level of alpha fetoprotein (AFP) (P=0.017),tumor,node,metastasis (TNM) staging(all P＜0.001),and negatively correlated with the degree of differentiation (P＜0.001).High expression of VEGF-C was positively correlated with TNM staging (P＜0.001).Cox multivariate analysis revealed that overall survival rate was significantly correlated with gender,AFP,degree of tumor differentiation,microvascular invasion,tumor diameter and high expression of CNTN-1 (P＜0.05-0.001).The recurrence-free survival was correlated with TNM staging,envelope integrity and high CNTN-1 expression (P＜0.05-0.001).Kaplan-Meier survival analysis revealed that postoperative overall survival curve and recurrence-free survival curve significantly differed between patients with high and low expression levels of CNTN-1 (both P＜0.01).Recurrence-free survival curve significantly differed between patients with high and low expression levels of VEGF-C (P=0.005).Conclusions CNTN-1 protein is highly expressed in HCC tissues and correlated with the expression of VEGF-C.It is associated with postoperative recurrence and metastasis of HCC after liver transplantation and affects the clinical prognosis of patients.
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ObjectiveTo investigate the biological significance and mechanism of VEGF-C in esophageal tumor development,and correlation of CNTN-1 level with VEGF-C.MethodsThe expression of VEGF-C and its receptors in esophageal squamous cancer cell (ESCC) and in corresponding noncancerous esophageal tissue specimens were detected by real-tithe PCR.Esophageal squamous cancer cell line TE-1 was transinfected by VEGF-C overexpression and gene silencing vectors,respectively,and the relative amount of C/EBP bound to CNTN-1 promoter was determined by quantitative ChIP,to explore the possibility that VEGF-C was involved in development of esophageal cancer through mediating transcription of CNTN-1.ResultsThe mRNA levels of VEGF-C was significantly higher in ESCC than in normal esophageal tissues.VEGF-C expression was significantly increased in VEGF-C-overexpressing TE-1 cells compared to untransfected cells (mock).Cells transfected with either of the VEGF-C targeting shRNA vectors,shRNA-1 and shRNA-2,showed reduced VEGF-C transcripts (P ＜ 0.01 ).Expression levels of VEGF-C and CNTN-1 mRNA correlated significantly with each other.The binding site of C/EBP in CNTN-1 was detected by ChIP,and the relative amount of C/EBP binding to CNTN-1 promoter was significantly increased in TE-1 after transfecting by VEGF-C overexpression vector ( P ＜ 0.05).ConclusionVEGF-C and its receptor are highly expressed in esophageal cancer tissues,which may be associated with ESCC carcinogenesis and development.VEGF-C may influence on growth and migration in TE-1 cells through CNTN-1.