RESEARCHOpenAccessCD103-positiveCSCexosomepromotesEMTofclearcellrenalcellcarcinoma:roleofremoteMiR-19b-3pLuWang1†,GuangYang2†,DanfengZhao1,JiaqiWang1,YangBai1,QiangPeng1,HongzhiWang1,RuizheFang1,GuangChen1,ZhichaoWang1,KeliangWang1,GuangbinLi1,YinhuiYang1,ZiqiWang1,PengyuGuo1,LiPeng1,DayongHou1andWanhaiXu1*AbstractBackground:Clearcellrenalcellcarcinoma(CCRCC)ischaracterizedbyahighlymetastaticpotential.Thestromalcommunicationbetweenstemcellsandcancercellscriticallyinfluencesmetastaticdisseminationofcancercells.Methods:Theeffectofexosomesisolatedfromcancerstemcells(CSCs)ofCCRCCpatientsontheprogressofepithelial-mesenchymaltransition(EMT)andlungmetastasisofCCRCCcellswereexamined.Results:CSCsexosomespromotedproliferationofCCRCCcellsandacceleratedtheprogressofEMT.BioactivemiR-19b-3ptransmittedtocancercellsbyCSCexosomesinducedEMTviarepressingtheexpressionofPTEN.CSCsexosomesderivedfromCCRCCpatientswithlungmetastasisproducedthestrongestpromotingeffectonEMT.Notably,CD103+CSCexosomeswereenrichedintumorcellsandinlungaswell,highlightingtheorganotropismconferredbyCD103.Inaddition,CD103+exosomeswereincreasedinbloodsamplesfromCCRCCpatientswithlungmetastasis.Conclusions:CSCexosomestransportedmiR-19b-3pintoCCRCCcellsandinitiatedEMTpromotingmetastasis.CD103+actedtoguideCSCexosomestotargetcancercellsandorgans,conferringthehighermetastaticcapacityofCCRCCtolungs,suggestingCD103+exosomesasapotentialmetastaticdiagnosticbiomarker.Keywords:Cancerstemcells,miR-19b-3p,Epithelial-mesenchymaltransition,CD103+exosomes,LungmetastasisBackgroundRenalcarcinomaisamongthe10mostcommoncan-cers,representing3.7%ofallnewcancercases.Theinci-dencehasbeenkeptrisingworldwideandtheprognosisremainspoor.Clearcellrenalcellcarcinoma(CCRCC),arenalcorticaltumorcharacterizedbymalignantepithe-lialcells,isthemostcommontypeofrenalcarcinomas,constituting80%ofallcases.Over30%ofpatientspresentwithmetastasisatthetimeofdiagnosis[1–3].Cancerstemcell(CSC)isacriticalfactorduringCCRCCdevelopmentbecauseitpromotesmetastaticspr...
