World journal of gastroenterology : WJG, 2014-12, Vol.20 (47), p.17894-17904
2014
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- Autor(en) / Beteiligte
- Titel
- HIF-1α induces VE-cadherin expression and modulates vasculogenic mimicry in esophageal carcinoma cells
- Ist Teil von
- World journal of gastroenterology : WJG, 2014-12, Vol.20 (47), p.17894-17904
- Ort / Verlag
- United States: Baishideng Publishing Group Inc
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1007-9327eISSN: 2219-2840DOI: 10.3748/wjg.v20.i47.17894Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4273139
- Format
- –
- Schlagworte
- Animals, Antigens, CD - genetics, Antigens, CD - metabolism, Apoptosis, Cadherins - genetics, Cadherins - metabolism, carcinoma, Carcinoma, Squamous Cell - blood supply, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - pathology, cell, Cell Line, Tumor, Cell Movement, Cell Proliferation, Esophageal, Esophageal Neoplasms - blood supply, Esophageal Neoplasms - genetics, Esophageal Neoplasms - metabolism, Esophageal Neoplasms - pathology, Esophageal Squamous Cell Carcinoma, Female, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-inducib, Hypoxia-Inducible Factor 1, alpha Subunit - genetics, Hypoxia-Inducible Factor 1, alpha Subunit - metabolism, Laminin - genetics, Laminin - metabolism, Mice, Inbred BALB C, Mice, Nude, Molecular Mimicry, Neoplasm Invasiveness, Neovascularization, Pathologic, Original, Receptor, EphA2 - genetics, Receptor, EphA2 - metabolism, RNA Interference, Signal Transduction, squamous, Time Factors, Transfection, Tumor Burden