时间 : 2009-12-03 07:18:13 来源:www.bioon.com
PublishedonlinebeforeprintJune4,2007,10.1073/pnas.0703478104PNAS|June12,2007|vol.104|no.24|10158-10163BIOLOGICALSCIENCES/MEDICALSCIENCES
Phenotypiccharacterizationofhumancolorectalcancerstemcells
PieroDalerba*,
*DepartmentofInternalMedicine,UniversityofMichigan,AnnArbor,MI48109;
CommunicatedbyIrvingL.Weissman,StanfordUniversitySchoolofMedicine,Stanford,CA,April24,2007(receivedforreviewNovember30,2006)
Recentobservationsindicatethat,inseveraltypesofhumancancer,onlyaphenotypicsubsetofcancercellswithineachtumoriscapableofinitiatingtumorgrowth.Thisfunctionalsubsetofcancercellsisoperationallydefinedasthe"cancerstemcell"(CSC)subset.HerewedevelopedaCSCmodelforthestudyofhumancolorectalcancer(CRC).SolidCRCtissues,eitherprimarytissuescollectedfromsurgicalspecimensorxenograftsestablishedinnonobesediabetic/severecombinedimmunodeficient(NOD/SCID)mice,weredisaggregatedintosingle-cellsuspensionsandanalyzedbyflowcytometry.Surfacemarkersthatdisplayedintratumorheterogeneousexpressionamongepithelialcancercellswereselectedforcellsortingandtumorigenicityexperiments.Individualphenotypiccancercellsubsetswerepurified,andtheirtumor-initiatingpropertieswereinvestigatedbyinjectioninNOD/SCIDmice.Ourobservationsindicatethat,insixofsixhumanCRCtested,theabilitytoengraftinvivoinimmunodeficientmicewasrestrictedtoaminoritysubpopulationofepithelialcelladhesionmolecule(EpCAM)high/CD44+epithelialcells.TumorsoriginatedfromEpCAMhigh/CD44+cellsmaintainedadifferentiatedphenotypeandreproducedthefullmorphologicandphenotypicheterogeneityoftheirparentallesions.AnalysisofthesurfacemoleculerepertoireofEpCAMhigh/CD44+cellsledtotheidentificationofCD166asanadditionaldifferentiallyexpressedmarker,usefulforCSCisolationinthreeofthreeCRCtested.TheseresultsvalidatethestemcellworkingmodelinhumanCRCandprovideahighlyrobustsurfacemarkerprofileforCRCstemcellisolation.
CD44|CD166/ALCAM|tumordifferentiation|tumorheterogeneityAgrowingbodyofevidenceisincreasinglylendingsupporttotheideathathumancancercanbeconsideredasastemcelldisease(1C3).Accordingtothe"cancerstemcell"(CSC)theory,tumorsarenottobeviewedassimplemonoclonalexpansionsoftransformedcells,butratherascomplextissueswhereabnormalgrowthisdrivenbyaminority,pathologicalCSCpoolthat,ontheonehand,hasacquiredtumor-relatedfeaturessuchasuncontrolledgrowthandtheabilitytoformmetastasesand,ontheotherhand,maintainsitsinherentcapacitytoself-renewanddifferentiateintoaphenotypicallyheterogeneous,althoughaberrant,progeny.Thishypothesisissupportedbythreekeyexperimentalobservationsinitiallyperformedonhumanacutemyeloidleukemia(4)andsubsequentlyextendedtohumansolidtumors(5,6):(i)Onlyaminorityofcancercellswithineachtumorisendowedwithtumorigenicpotentialwhentransplantedintoimmunodeficientmice,(ii)tumorigeniccancercellsarecharacterizedbyadistinctiveprofileofsurfacemarkersandcanbedifferentiallyandreproduciblyisolatedfromnontumorigeniconesbyflowcytometry,and(iii)tumorsgrownfromtumorigeniccellscontainmixedpopulationsofbothtumorigenicandnontumorigeniccancercells,thusre-creatingthefullphenotypicheterogeneityoftheparenttumor.Currently,cancercellsubpopulationsselectivelyendowedwithtumorigenicpotentialareoperationallydefinedasCSCsandhavebeenprospectivelyidentifiedfromselectedtypesofhumansolidcancer,suchasbreast(5),brain(6,7),colon(8,9),headandneck(10),andpancreaticcancer(11).However,theCSCworkingmodelisstillbeingsubjectedtointensedebate(12),anddatapublishedoncolorectalcancer(CRC)indicatethatasubgroupofprimaryCRCislikelytobenegativeforthemarkercurrentlyusedforisolationofcolorectalCSCs(Co-CSCs)(9).Inthepresentstudy,wedevelopedanalternative,veryrobustprotocolfortheisolationofhumanCo-CSCs.全文链接:http://www.pnas.org/cgi/content/full/104/24/10158?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=Michael++Clarke&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT相关报道:韩伟:肿瘤干细胞为癌症治疗带来新曙光癌症的靶向治疗瞄准肿瘤干细胞NatureGenetics:肿瘤的干细胞来源学说获得新支持干细胞可治疗脑肿瘤肿瘤中是否存在癌症干细胞Nature:研究称癌症也有类似干细胞疑似肿瘤细胞源泉研究人员从肿瘤中发现出的新的前癌干细胞用干细胞追踪肿瘤、传递药物
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