Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties 英文参考文献.docVIP

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Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties 英文参考文献.doc

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Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties 英文参考文献

Non-SmallCellLungCancerCellsExpressingCD44Are EnrichedforStemCell-LikeProperties ElaineLai-HanLeung1,RonaldR.Fiscus2,3,JamesW.Tung4,VickyPui-ChiTin1,LikCheungCheng5 ,Alan Dart-LoonSihoe5,LouisM.Fink4,YupoMa4,6,MariaPikWong1* 1DepartmentofPathology,TheUniversityofHongKong,HongKong,SpecialAdministrativeRegion,China,2CancerMolecularBiologySection,NevadaCancerInstitute, Las Vegas, Nevada, United States of America, 3College of Pharmacy, University of Southern Nevada, Henderson, Nevada, United States of America, 4Division of Laboratory Medicine, Nevada Cancer Institute,Las Vegas, Nevada, United States ofAmerica, 5Cardiothoracic Surgery Unit, Queen MaryHospital,Hong Kong, Special AdministrativeRegion,China,6DepartmentofPathology,StonyBrookUniversityMedicalCenter,StonyBrook,NewYork,UnitedStatesofAmerica Abstract Background:Thecancerstemcelltheoryhypothesizesthatcancersareperpetuatedbycancerstemcells(CSC)ortumor initiatingcells(TIC)possessingself-renewalandotherstemcell-likepropertieswhiledifferentiatednon-stem/initiatingcells haveafinitelifespan.Toinvestigatewhetherthehypothesisisapplicabletolungcancer,identificationoflungCSCand demonstrationofthesecapacitiesisessential. Methodology/Principal Finding: The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) werescreenedbyflowcytometryin10lungcancercelllines.CD44wasfurtherinvestigatedbytestingforinvitroandinvivo tumorigenecity.FormationofspheroidbodiesandinvivotumorinitiationabilityweredemonstratedinCD44 cellsof4cell + lines.SerialinvivotumortransplantabilityinnudemicewasdemonstratedusingH1299cellline.Theprimaryxenografts initiated from CD44+ cells consisted of mixed CD44+ and CD442 cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44 and CD44 cells derived from CD44 -initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2 . These + + + + stemness markers