Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System 英文参考文献.docVIP

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Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System 英文参考文献.doc

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Establishment and Characterization of a Highly Tumourigenic and Cancer Stem Cell Enriched Pancreatic Cancer Cell Line as a Well Defined Model System 英文参考文献

EstablishmentandCharacterizationofaHighly TumourigenicandCancerStemCellEnrichedPancreatic CancerCellLineasaWellDefinedModelSystem JohannesFredebohm1*,MichaelBoettcher1,ChristianEisen2,MatthiasM.Gaida3,AnetteHeller4, ShereenKeleg4,Jo¨rgTost5,KarinM.Greulich-Bode6,AgnesHotz-Wagenblatt7,MarkLathrop5, NathaliaA.Giese4,Jo¨rgD.Hoheisel1 1Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg,Germany,3InstituteofPathology,UniversityHospitalofHeidelberg,Heidelberg,Germany,4EuropeanPancreasCenter,UniversityHospitalofHeidelberg, Heidelberg,Germany,5InstitutdeGe′nomique,CentreNationaldeGe′notypage, Evry,France,6GeneticsofSkinCarcinogenesis,GermanCancerResearchCenter(DKFZ), Heidelberg,Germany,7FunctionalProteomeAnalysis,GermanCancerResearchCenter(DKFZ),Heidelberg,Germany Abstract Standardcancercelllinesdonotmodeltheintratumouralheterogeneitysituationsufficiently.Clonalselectionleadstoa homogeneous population of cells by genetic drift. Heterogeneity of tumour cells, however, is particularly critical for therapeuticallyrelevantstudies,sinceitisaprerequisiteforacquiringdrugresistanceandreoccurrenceoftumours.Here, we report the isolation of a highly tumourigenic primary pancreatic cancer cell line, called JoPaca-1 and its detailed characterization at multiple levels. Implantation of as few as 100 JoPaca-1 cells into immunodeficient mice gave rise to tumoursthatwerehistologicallyverysimilartotheprimarytumour.ThehighheterogeneityofJoPaca-1wasreflectedby diversecellmorphologyandasubstantialnumberofchromosomalaberrations.Comparativewhole-genomesequencingof JoPaca-1andBxPC-3revealedmutationsingenesfrequentlyalteredinpancreaticcancer.Exceptionallyhighexpressionof cancerstemcellmarkersandahighclonogenicpotentialinvitroandinvivowasobserved.Alloftheseattributesmakethis celllineanextremelyvaluablemodeltostudythebiologyofandpharmaceuticaleffectsonpancreaticcancer. Citation:FredebohmJ