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1、PriorityReportTargetingCancerStemCellsthroughL1CAMSuppressesGliomaGrowth1,5,61,51,51,51,5ShidengBao,QiulianWu,ZhizhongLi,SithSathornsumetee,HuiWang,2,51,51,3,4,5RogerE.McLendon,AnitaB.Hjelmeland,andJeremyN.RichDepartmentsof1Surgery,2Pathology,3Medicine
2、,and4PharmacologyandCancerBiology,and5PrestonRobertTischBrainTumorCenter,DukeUniversityMedicalCenter,Durham,NorthCarolina;and6DepartmentsofRadiationOncologyandNeurosurgery,UniversityofColoradoDenverSchoolofMedicine,Aurora,ColoradoAbstractbiopsyspecimen
3、susingthecellsurfacemarkerCD133(prominin1)althoughtherearetumorsthatmaycontainCD133tumor-Malignantgliomasarelethalcancersthatdisplaystrikinginitiatingcells(6,7),albeitoftenwithlowertumorpotency.Wecellularheterogeneity.Ahighlytumorigenicgliomatumor+pre
4、viouslyshowedthatCD133gliomacellsderivedfromhumansubpopulation,termedcancerstemcellsortumor-initiatingtumorsareradioresistant(5),promoteangiogenesis(6),anddisplaycells,promotestherapeuticresistanceandtumorangiogene-greatertumorigenicpotentialinimmunoco
5、mpromisedmicesis.Therefore,targetingcancerstemcellsmayimprove+relativetoCD133gliomacells(5).Thus,targetingCD133gliomapatientsurvival.Weinterrogatedtheroleofaneuronalcellcellsurvivalandprotumorigenicbehaviorsbyidentifyingnoveladhesionmolecule,L1CAM,ing
6、liomastemcellsasL1CAMmoleculartargetsspecificincancerstemcellsmayimprovepatientregulatesbraindevelopmentandisexpressedingliomas.++outcome.L1CAMandCD133cellscosegregatedingliomas,andlevels+MoleculartargetsthataresecretedorlocatedonthecellsurfaceofL1CAMw
7、erehigherinCD133gliomacellsthannormalareparticularlyenticingasantibodyandsmall-moleculeinhibitorneuralprogenitors.TargetingL1CAMusinglentiviral-mediat-+therapiesthatdonothavetocrossthecellmembraneandcanbeedshorthairpinRNA(shRNA)interferenceinCD133gliom
8、adevelopedforclinicaluse.Toselectapotentialtarget,weconsultedcellspotentlydisruptedneurosphereformation,inducedtheliteraturetoselectacellsurfaceproteinthathasbeenreportedapoptosis,andinhibitedgrowthspecificallyingliomastemtobeexpressedi