Annexin A2 Promotes the Migration and Invasion of Human Hepatocellular Carcinoma Cells In Vitro by Regulating the Shedding of CD147-Harboring Microvesicles from Tumor Cells.docVIP

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Annexin A2 Promotes the Migration and Invasion of Human Hepatocellular Carcinoma Cells In Vitro by Regulating the Shedding of CD147-Harboring Microvesicles from Tumor Cells.doc

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Annexin A2 Promotes the Migration and Invasion of Human Hepatocellular Carcinoma Cells In Vitro by Regulating the Shedding of CD147-Harboring Microvesicles from Tumor Cells

AnnexinA2PromotestheMigrationandInvasionof HumanHepatocellularCarcinomaCellsInVitroby RegulatingtheSheddingofCD147-Harboring MicrovesiclesfromTumorCells WeiZhang1,2.,PuZhao3,4.,Xiu-LiXu5.,LeiCai1,Zhen-ShunSong1,Da-YongCao1,Kai-ShanTao1 ,Wen- PingZhou2*,Zhi-NanChen4*,Ke-FengDou1* 1DepartmentofHepatobiliarySurgery,XijingHospital,FourthMilitaryMedicalUniversity,Xi’an,ShaanxiProvince,China,2DepartmentofHepatobiliarySurgery,General HospitalofShenyangMilitaryAreaCommand,Shenyang,LiaoningProvince,China,3CollegeofLifeandHealthSciences,NortheasternUniversity,Shenyang,Liaoning Province,China,4CellEngineeringResearchCenterandDepartmentofCellBiology,StateKeyLaboratoryofCancerBiology,StateKeyDisciplineofCellUniversity,Fourth MilitaryMedicalUniversity,Xi’an,ShaanxiProvince,China,5CenterofClinicalLaboratoryMedicineofPeople’sLiberationArmy,XijingHospital,FourthMilitaryMedical University,Xi’an,ShaanxiProvince,China Abstract IthasbeenreportedthatAnnexinA2(ANXA2)isup-regulatedinhepatocellularcarcinoma(HCC),buttherolesofANXA2in themigrationandinvasionofHCCcellshavenotbeendetermined.Inthisstudy,wefoundthatANXA2-specificsiRNA(si- ANXA2)significantlyinhibitedthemigrationandinvasionofHCCcellsco-culturedwithfibroblastsinvitro.Inaddition,the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated.ANXA2wasalsofoundtobeco-localizedandco-immunoprecipitatedwithCD147.Furtherinvestigation revealedthattheexpressionofANXA2inHCCcellsaffectedthesheddingofCD147-harboringmembranemicrovesicles, actingasavehicleforCD147intumor-stromalinteractionsandtherebyregulatingtheproductionofMMP-2byfibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulatingthetraffickingofCD147-harboringmembranemicrovesicles. Citation:ZhangW,ZhaoP,XuX-L,CaiL,SongZ-S,etal.(2013)AnnexinA2PromotestheMigrationandInvasionofHumanHepatocellularCarcinomaCellsIn VitrobyRegulatingtheSheddi