中文摘要：

AIM:To investigate whether hypoxia inducible factor(HIF)-1αmodulates vasculogenic mimicry(VM)by upregulating VE-cadherin expression in esophageal squamous cell carcinoma(ESCC).METHODS:Esophageal squamous cancer cell lines Eca109 and TE13 were transfected with plasmids harboring small interfering RNAs targeting HIF-1αor VEcadherin.The proliferation and invasion of esophageal carcinoma cells were detected by MTT and Transwell migration assays.The formation of tubular networks of cells was analyzed by 3D culture in vitro.BALB/c nude mice were used to observe xenograft tumor formation.The relationship between the expression of HIF-1αand VE-cadherin,ephrin A2(Eph A2)and laminin5γ2(LN5γ2)was measured by Western blot and real-time polymerase chain reaction.RESULTS:Knockdown of HIF-1αinhibited cell proliferation(32.3%±6.1%for Eca109 cells and 38.6%±6.8%for TE13 cells,P【0.05).Both Eca109 and TE13cells formed typical tubular networks.The number of tubular networks markedly decreased when HIF-1αor VE-cadherin was knocked down.Expression of VEcadherin,Eph A2 and LN5γ2 was dramatically inhibited,but the expression of matrix metalloproteinase 2 had no obvious change in HIF-1α-silenced cells.Knockdown of VE-cadherin significantly decreased expression of both Eph A2 and LN5γ2(P【0.05),while HIF-1αexpression was unchanged.The time for xenograft tumor formation was 6±1.2 d for Eca109 cells and Eca109cells transfected with HIF-1αNeo control short hairpin RNA(sh RNA)vector,and 8.4±2.1 d for Eca109 cells transfected with an sh RNA against HIF-1α.Knockdown of HIF-1αinhibited vasculogenic mimicry(VM)and tumorigenicity in vivo.CONCLUSION:HIF-1αmay modulate VM in ESCC by regulating VE-cadherin expression,which affects VM formation through Eph A2 and LN5γ2.

英文摘要：

AIM: To investigate whether hypoxia inducible factor (HIF)-1α modulates vasculogenic mimicry (VM) by upregulating VE-cadherin expression in esophageal squamous cell carcinoma (ESCC).