ContentslistsavailableatScienceDirectSeminarsinCancerBiologyjournalhomepage:www.elsevier.com/locate/semcancerReviewThemultifacetedroleofmesenchymalstemcellsincancerMichaelTimanera,KelvinKTsaib,c,YuvalShakeda,⁎aTechnion-IntegeratedCancerCenter,CellBiologyandCancerScience,RappaportFacultyofMedicine,Technion-IsraelInstituteofTechnology,Haifa,IsraelbLaboratoryofAdvancedMolecularTherapeutics,andDivisionofGastroenterology,WanFangHospital,andGraduateInstitutesofClinicalMedicine,CollegeofMedicine,TaipeiMedicalUniversity,TaipeiTaiwancNationalInstituteofCancerResearch,NationalHealthResearchInstitutes,TaiwanARTICLEINFOKeywords:ImmunosuppressionAngiogenesisMesenchymalstemcellsResistanceMetastasisABSTRACTMesenchymalstemcells(MSCs)aremultipotentstemcellsderivedfromthemesodermthatgiverisetoseveralmesenchymallineages,includingosteoblasts,adipocytes,chondrocytesandmyocytes.TheirpotentabilitytohometotumorscoupledwiththeirdifferentiationpotentialandimmunosuppressivefunctionpositionsMSCsaskeyregulatorsoftumorfate.HerewereviewtheexistingknowledgeontheinvolvementofMSCsinmultipletumor-promotingprocesses,includingangiogenesis,epithelial-mesenchymaltransition,metastasis,im-munosuppressionandtherapyresistance.WealsodiscusstheclinicalpotentialofMSC-basedtherapyforcancer.1.IntroductionMesenchymalstemcells(MSCs),alsoknownasmesenchymalstromalcells,aremultipotentstemcellswithhighdifferentiationpo-tentialandself-renewalabilities[1,2].MSCswerefirstisolatedfromadultbonemarrowinthelate1960sandweredefinedasfibroblast-likecells[3,4].Onlyin1991,CaplanandcolleaguestermedthemMSCsbasedontheirdifferentiationpattern[5,6].MSCsgiverisetoseveralmesenchymaltissues,astheydifferentiateintomultiplecelltypessuchasosteoblasts,chondroblasts,myocytesandadipocytes[5,7,8].Fur-thermore,MSCsarealsoabletotransdifferentiateinvitrointoen-dodermal(epithelial)andectodermal(neuronal)lineagesundercertaincultureconditions[9–11].Accordingtomostclinicalstudies,themainsourceofMSCsisthebonemarrowwheretheyexistinlowabundance,makin...
