Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells 英文参考文献.docVIP

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Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells 英文参考文献.doc

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Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells 英文参考文献

DirectInVivoEvidenceforTumorPropagationby GlioblastomaCancerStemCells JustinD.Lathia1*,JosephGallagher1,JayT.Myers2,MeizhangLi1,AmitVasanji3¤,RogerE.McLendon4, AnitaB.Hjelmeland1,5,AlexY.Huang2,JeremyN.Rich1,5* 1DepartmentofStemCellBiologyandRegenerativeMedicine,LernerResearchInstitute,ClevelandClinic,Cleveland,Ohio,UnitedStatesofAmerica,2Departmentof Pediatrics,CaseWesternReserveUniversitySchoolofMedicine,Cleveland,Ohio,UnitedStatesofAmerica,3ImageProcessingCore,LernerResearchInstitute,Cleveland Clinic, Cleveland, Ohio, United States of America, 4Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America, 5Molecular MedicineProgram, Cleveland Clinic Lerner College of Medicine at CaseWestern Reserve University School of Medicine, Cleveland, Ohio, United States of America Abstract High-gradegliomas(WorldHealthOrganizationgradeIIIanaplasticastrocytomaandgradeIVglioblastomamultiforme),the mostprevalentprimarymalignantbraintumors,displayacellularhierarchywithself-renewing,tumorigeniccancerstem cells (CSCs) at the apex. While the CSC hypothesis has been an attractive model to describe many aspects of tumor behavior,itremainscontroversialduetounresolvedissuesincludingtheuseofexvivoanalyseswithdifferentialgrowth conditions.ACSCpopulationhasbeenconfirmedinmalignantgliomasbypreferentialtumorformationfromcellsdirectly isolatedfrompatientbiopsyspecimens.However,directcomparisonofmultipletumorcellpopulationswithanalysisofthe resulting phenotypes of each population within a representative tumor environment has not been clearly described. To directly test the relative tumorigenic potential of CSCs and non-stem tumor cells in the same microenvironment, we interrogatedmatchedtumorpopulationspurifiedfromaprimaryhumantumortransplantedintoaxenograftmousemodel andmonitoredcompetitiveinvivotumorgrowthstudiesusingserialinvivointravitalmicroscopy.WhileCSCswereasmall minorityoftheinitialtransplantedcancercellpopulation,theCSCs,notthenon-stem