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1、Zhengetal.JournalofExperimental&ClinicalCancerResearch2010,29:31http://www.jeccr.com/content/29/1/31RESEARCHOpenAccessChemokinereceptorCXCR7regulatestheinvasion,angiogenesisandtumorgrowthofhumanhepatocellularcarcinomacells*KeZheng,Hong-YuanLi,Xin-LiangSu,Xiao-YiWa
2、ng,TianTian,FanLi,Guo-ShengRenAbstractBackground:Inspiteofrecentadvancesindiagnosticandtherapeuticmeasures,theprognosisofhepatocellularcarcinoma(HCC)patientsremainspoor.Therefore,itiscrucialtounderstandwhatfactorsareinvolvedinpromotingdevelopmentofHCC.Evidenceisac
3、cumulatingthatmembersofthechemokinereceptorfamilyareviewedaspromisingtherapeutictargetsinthefightagainstcancer.MorerecentstudieshaverevealedthatchemokinereceptorCXCR7playsanimportantroleincancerdevelopment.However,littleisknownabouttheeffectofCXCR7ontheprocessofHC
4、Ccellinvasionandangiogenesis.TheaimofthisstudyistoinvestigatetheexpressionofCXCR7inhepatocellularcarcinomatissuesandcelllinesandtoevaluatetheroleofCXCR7intumorgrowth,angiogenesisandinvasionofHCCcells.Methods:WeconstructedCXCR7expressingshRNA,andCXCR7shRNAwassubseq
5、uentlystablytransfectedintohumanHCCcells.WeevaluatedtheeffectofCXCR7inhibitiononcellinvasion,adhesion,VEGFsecretion,tubeformationandtumorgrowth.ImmunohistochemistrywasdonetoassesstheexpressionofCXCR7inhumanhepatocellularcarcinomatissuesandCD31intumorofmice.Wealsoe
6、valuatedtheeffectofVEGFstimulationonexpressionofCXCR7.Results:CXCR7wasoverexpressedinhepatocellularcarcinomatissues.WeshowedthathighinvasivepotentialHCCcelllinesexpresshighlevelsofCXCR7.Invitro,CXCL12wasfoundtoinduceinvasion,adhesion,tubeformation,andVEGFsecretion
7、inSMMC-7721cells.ThesebiologicaleffectswereinhibitedbysilencingofCXCR7inSMMC-7721cells.Inaddition,wealsofoundthatVEGFstimulationcanup-regulateCXCR7expressioninSMMC-7721cellsandHUVECs.Moreimportantly,enhancedexpressionofCXCR7byVEGFwasfounctional.Invivo,tumorgrowtha
8、ndangiogenesisweresuppressedbyknockdownofCXCR7inSMMC-7721cells.However,silencingofCXCR7didnotaffectmetastasisoftumorinvivo.Conclusions:IncreasedCXCR7exp
