Exosomesfromhumanadipose-derivedmesenchymalstemcellspromotemigrationthroughWntsignalingpathwayinabreastcancercellmodel|SpringerLink
Abstract

Humanmesenchymalstemcell(MSC)-conditionedmedium(CM)waspreviouslyreportedtoaffectthebiologyoftumorcells;however,theprecisemechanismsremainunclear.Here,weshowthatMSCssecreted40–100 nmparticles,whichhavethetypicalcharacteristicsofexosomes,andtheseMSC-derivedexosomespromotedmigrationofthebreastcancercelllineMCF7.Globalgeneexpressionprofilingrevealedthatseveralcancer-relatedsignalingpathwayswereupregulatedafterexosometreatmentinMCF7,andtheWntsignalingpathwaywasfurtherconfirmedtobeactivated.OurfindingsdemonstratedanewmechanismthroughwhichMSC-CMmaycontributetotumorcellmigration.

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Acknowledgments

ThisstudywassupportedbygrantsfromNationalNaturalScienceFoundationofChina(No.30830052,30700321,and30800429)andProgramforCheungKongScholarsandInnovativeResearchTeaminUniversity-PCSIRT(No.IRT0909).

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AuthorinformationAffiliationsCenterofExcellenceinTissueEngineering,InstituteofBasicMedicalSciencesandSchoolofBasicMedicine,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing,People’sRepublicofChinaRuizhuLin, ShihuaWang  RobertChunhuaZhaoPekingUnionMedicalCollegeHospital,Beijing,People’sRepublicofChinaRobertChunhuaZhaoAuthorsRuizhuLinViewauthorpublicationsYoucanalsosearchforthisauthorinPubMedGoogleScholarShihuaWangViewauthorpublicationsYoucanalsosearchforthisauthorinPubMedGoogleScholarRobertChunhuaZhaoViewauthorpublicationsYoucanalsosearchforthisauthorinPubMedGoogleScholarCorrespondingauthor

CorrespondencetoRobertChunhuaZhao.

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RuizhuLinandShihuaWanghavecontributedequallytothisstudy.

Electronicsupplementarymaterial

Belowisthelinktotheelectronicsupplementarymaterial.Fig. 1

MigrationcapacityofMCF7wasreducedinMSCculturemediumwithoutexosome.MCF7pretreatedwithoriginalMSCculturemediumandtheMSCculturemediumwithoutexosomefor24handwerethensubjectedto(A)woundrepairassays.Thewoundwasgeneratedattime0handcellmigrationintothewoundwasanalyzedbyphase-contrastmicroscopyat18h.Oneof3independentexperimentsisshownhere:(B)modifiedBoydenchamberassays.Thenumberofcellsthatmigratedtothebottomoftheinsertmembranewasquantifiedafterstainingwithcrystalviolet.Representativeimagesareshownattop.Graphsinthebottomindicatetheaveragenumberofcellsdemonstratedasabsorbanceatthebottomoftheinsertmembrane(TIFF4407kb)

Fig. 2

Geneontologyanalysisof(A)genesassociatedwithepithelialcellmigration(GO0010631)or(B)genesassociatedwithcellmigration(GO0016477)(TIFF2577kb)

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Lin,R.,Wang,S.Zhao,R.C.Exosomesfromhumanadipose-derivedmesenchymalstemcellspromotemigrationthroughWntsignalingpathwayinabreastcancercellmodel.MolCellBiochem383,13–20(2013).https://doi.org/10.1007/s11010-013-1746-z

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Received:11April2013

Accepted:19June2013

Published:29June2013

IssueDate:November2013

DOI:https://doi.org/10.1007/s11010-013-1746-z

KeywordsExosomeMesenchymalstemcellMCF7WntMigration