Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer 英文参考文献.docVIP

SecretedProteinAcidicandRichinCysteine(SPARC) SuppressesAngiogenesisbyDown-Regulatingthe ExpressionofVEGFandMMP-7inGastricCancer Jun-LingZhang.,Guo-WeiChen.,Yu-CunLiu*,Peng-YuanWang,XinWang,Yuan-LianWan,JingZhu, Hong-QiaoGao,JieYin,WeiWang,Mao-LinTian DepartmentofGeneralSurgery,PekingUniversityFirstHospital,Beijing,People’sRepublicofChina Abstract Background:Secretedproteinacidicandrichincysteine(SPARC)isaglycoproteinthatfunctionstoinhibitangiogenesis, proliferation,andinvasionindifferenttypesofcancer.TheabilityofSPARCtomodulateneovascularisationisbelievedtobe mediated in part by its ability to modulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases(MMPs).Inthisstudy,weaimedtodeterminetheeffectofSPARCexpressioningastriccancercellson proliferationandangiogenesisinvitroandinvivo. Method: We evaluated expression of SPARC in seven human gastric cancer cell lines. Then we established a stably transfectedSPARCoverexpressedcellline(BGC-SP)andastablytransfectedSPARCknock-downcellline(HGC-sh).Theeffect ofSPARCoverexpressionandSPARCsilencingwasstudiedbyexaminingcapillaryformationofHUVECsinvitroandadorsal skin-fold chamber model in vivo. Quantitative real-time PCR and western blotting were performed to detect if the expressionsofVEGFandMMP-7weremodulatedbySPARCexpression.TofurtherdeterminetheeffectofSPARCexpression on angiogenesis in vivo, xenograft models were established and microvessel density (MVD) of different clones were detectedbyimmunohistochemistry. Results: Endogenous SPARC overexpression inhibited the expression of VEGF and MMP-7, as well as the angiogenesis induced by BGC-SP cells. Correspondingly, SPARC silencing increased the expressionof VEGF andMMP-7, as well as the angiogenesisinducedbyHGC-shcells.ElevatedangiogenesisinducedbySPARCsilencinginHGC-shcellswasdecreased whenVEGFwasneutralisedbyantibodies,andMMP-7wasknockeddowninvitro. Conclusion:SPARCsuppressesangiogenesisofgastriccancerbydown-regulatingtheexpressionofVE