PNAS：结肠癌和直肠癌中发现肿瘤干细胞

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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