肿瘤干细胞研究进展_于欣

ChinaBiotechnology,2010,30(1):80-84于欣乔守怡*(200433)肿瘤干细胞(cancerstemcel,lCSC)假说是近年来提出的关于肿瘤发生的新理论,在所有的肿瘤细胞中,可能只有一小部分细胞具有产生肿瘤并维持肿瘤生长和异质性的能力,目前已经在白血病乳腺癌脑癌等肿瘤组织中成功分离出了肿瘤干细胞,深入了解肿瘤干细胞的生物学特性发展相应的鉴别方法以及特殊的治疗手段对癌症的临床治疗有着重要的意义主要从肿瘤干细胞的概念起源鉴定分离方法与正常干细胞的比较比率以及与肿瘤转移的关系等方面进行了综述肿瘤干细胞干细胞起源比率肿瘤转移Q813:2009-09-14:2009-10-29*,:[e-mail],,,,,,,1,,DNA,,,,,,[1],,:,,Mackillop[2]1983,1997Bonnet[3](acutemyeloidleukaemia,AML)CD34+CD38-,AML0.2%,/(NOD/SCID),AML,AMLNOD/SCIDAMLCD34+CD38-AML,,AML,,[4][5][6-7][8][9][10],22.1,DOI10.13523/j.cb.201001152010,30(1):,,,[1,11],[12]2.2,[13],,p21CIP1p18INK4C,,,,,,,,[14-15]3,:3.1,,,,,,,,,[16-17][18],[19-20],3.2,Bcl-2BCR/ABL[21]-Wnt/B-catenin[22]MLL-AF9-[23]ETV6-RUNX1p190BCRABL,(ALL)CD34+CD38-CD19+BCD34+CD38-CD19+NOD/SCID,ALL,CD34+CD38-CD19-[24][25]3.3,[26],(bonemarrowderivedcells,BMDCs)(neoplasticepitheliun)[27],CD44,[28]4[29],,-,,[30],[31],,,,(fluorescence-activatedcellsorting,FACS)81ChinaBiotechnologyVo.l30No.12010(magneticactivatedcellsorting,MACS),[3-5](acutemyeloidleukaemia,AML)B(acutelymphoblasticleukemia,B-ALL)(blast-crisischronicmyelocyticleukemia,blast-crisisCML)(glioblastoma)(medulloblastoma)(pilocyticastrocytoma)(anaplasticependymoma)[3-8,30],(aldehydedehydrogenase,ALDH),ALDEFLUOR[32]26S[33],[34]NOD/SCID,NOD/SCID,,,NOD/SCID[35]5NOD/SCID,0.1%,[3-8]Kelly[36],10%Quintana[37]NOD/SCID-2C(immunocompromisedNOD/SCIDinterleukin-2receptorgammachainnullmice,II2rg-/-),25%,Schatton[38]NOD/SCID,0.0001%,,,[39]6,,,,,90%,,[40],,,,[41],[42],,,[43],,,,,[41]7,,,,,822010,30(1):[44-46],,,[47],,Gupta16000(salinomycin),(paclitaxel),[48]8,,,,,[1]ReyaT,MorrisonSJ,ClarkeMF,eta.lStemcells,cancer,andcancerstemcells.Nature,2001,414:105-111.[2]MackillopWJ,CiampiA,TillJE,eta.lAstemcellmodelofhumantumorgrowth,implicationsfortumorcellclonogenicassays.JournaloftheNationalCancerInstitute,1983,70:9-16.[3]BonnetD,DickJE.Humanacutemyeloidleukemiaisorganizedasahierarchythatoriginatesfromaprimitivehematopoieticcel.lNatureMedicine,1997,3(7):730-737.[4]AI-HajjM,WichaMS,Benito-HernandezA,eta.lProspectiveidentificationoftumorigenicbreastcancercells.ProceedingsoftheNationalAcademyofSciences,2003,100(7):3983-3988.[5]SinghSK,ClarkeID,TeraskiM,eta.lIdentificationofhumanbraintumourinitiatingcells.Nature,2004,432:386-401.[6]Ricci-VitianiL,LombardiDG,PilozziE,eta.lIdentificationandexpansionofhumancoloncancerinitiatingcells.Nature,2007,445(7123):111-115.[7]O.BrienCA,PollettA,GallingerS,eta.lAhumancoloncancercellcapableofinitiatingtumourgrowthinimmunodeficientmice.Nature,2007,445(7123)106-110.[8]CollinsAT,BerryPA,HydeC,eta.lProspectiveidentificationoftumorigenicprostatecancerstemcells.CancerResearch,2005,65(23):10946-10951.[9]LiC,HeidtDG,DalerbaP,eta.lIdentificationofpancreaticcancerstemcells.CancerResearch,2007,67:1030-1037.[10]YangZF,HoDW,NgMN,eta.lSignificanceofCD90+cancerstemcellsinhumanlivercancer.CancerCel,l2008,13:153-166.[11]DonovanPJ,GearhartJ.Theendofthebeginningforpluripotentstemcells.Nature,2001,414:92-97.[12]IwasakiH,SudaT.Cancerstemcellsandtheirniche.CancerScience,2009,100(7):1166-1172.[13]GuoW,LaskyJL,WuH.Cancerstemcells.InternationalPediatricResearchFoundation,2006,59(4):59-64.[14]ChenT,RodriguesN,ShenH,eta.lHematopoieticstemcellquiescencemaintainedbyp21cip1/waf1.Science,2000,287:1804-1808.[15]YuanY,ShenH,FranklinDS,eta.lInvivoself-renewingdivisionsofhaematopoieticstemcellsareincreasedintheabsenceoftheearlyG1-phaseinhibitor,p18INK4C.NatureCellBiology,2004,6:436-442.[16]AyyananA,CivenniG,CiarloniL,eta.lIncreasedwntsignalingtriggersoncogenicconversionofhumanbreastepithelialcellsbyaNotch-dependentmechanism.ProceedingsoftheNationalAcademyofSciences,2006,103(10):3799-3804.[17]KnudsonAG,StrongLC,AndersonDE,Heredityandcancerinman.ProgressinMedicalGenetics,1973,9:113-158.[18]ShackletonM,VaillantF,SimpsonKJ,eta.lGenerationofafunctionalmammaryglandfromasinglestemcel.lNature,2006,439:84-88.[19]KimCF,JacksonEL,WoolfendenAE,eta.lIdentificationofbronchioalveolarstemcellsinnormallungandlungcancer.Cel,l2005,121:823-835.[20]MiyamotoT,WeissmanIL,AkashiK.AML1/ETO-expressingnonleukemicstemcellsinacutemyelogenousleukemiawith8;21chromosomaltranslocation.ProceedingsoftheNationalAcademyofSciences,2000,97:7521-7526.[21]JaiswalS,TraverD,MiyamotoT,eta.lExpressionofBCR/ABLandBCL-2inmyeloidprogenitorsleadstomyeloidleukemias.ProceedingsoftheNationalAcademyofSciences,2003,100:10002-10007.[22]JamiesonCH,AillesLE,DyllaSJ,eta.lGranulocyte-macrophageprogenitorsascandidateleukemicstemcellsinblast-crisisCML.TheNewEnglandJournalofMedicine,2004,351:657-667.[23]KrivstovAV,TwomeyD,FengZ,eta.lTransformationfromcommittedprogenitortoleukaemiastemcellinitiatedbyMLL-AF9.Nature,2006,442:818-822.[24]CastorA,NilssonL,Astrand-GrundstromI,eta.lDistinctpatternsofhematopoieticstemcellinvolvementinacutelymphoblasticleukemia.NatureMedicine,2005,11(6):630-637.83ChinaBiotechnologyVo.l30No.12010[25]VescoviAL,GalliR,ReynoldsBA.Braintumorstemcells.NatureReviewsCancer,2006,6:425-436.[26]WagersAJ,WeissmanIL.Plasticityofadultstemcells.Cel,l2004,116:639-648.[27]RizviAZ,SwainJR,Dav