CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients 英文参考文献.docVIP

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CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients 英文参考文献.doc

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CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an Undifferentiated Phenotype in Patients 英文参考文献

CD57high NeuroblastomaCellsHaveAggressive AttributesExSituandanUndifferentiatedPhenotypein Patients Anne-MarieSchlitter1.,CarmenDorneburg1.,ThomasF.E.Barth2,JoachimWahl1,JohannesH.Schulte3, SilkeBru¨derlein2,Klaus-MichaelDebatin1,ChristianBeltinger1* 1Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany, 2Institute of Pathology, University Medical Center Ulm, Ulm, Germany,3PediatricHematologyandOncology,UniversityChildren’sHospitalEssen,Essen,Germany Abstract Background: Neuroblastomais thoughttooriginatefromneuralcrest-derived cells. CD57definesmigratoryneural crest cellsinnormaldevelopmentandisexpressedinneuroblastoma. MethodologyandPrincipalFindings:WeinvestigatedtheroleofCD57expressioninneuroblastomacellsexsituandin situ. Compared to CD57low U-NB1 neuroblastoma cells, CD57high cells developed tumors with decreased latency after orthotopictransplantationintoadrenalglandsofmice.Inaddition,CD57high U-NB1andSK-N-BE(2)-Cneuroblastomacells were also more clonogenic, induced more spheres and were less lineage-restricted. CD57high cells attached better to endothelialcellsandshowedenhancedinvasiveness.WhileinvasionofU-NB1cellswasinhibitedbyblockingantibodies againstCD57,neitherinvasionofSK-N-BE(2)-CcellsnoradhesionofU-NB1andSK-N-BE(2)-Ccellswasattenuated.Aftertail veininjectiononlyCD57highcellsgeneratedlivermetastases,whileoverallmetastaticratewasnotincreasedascomparedto CD57low cells.Instroma-poorneuroblastomaofpatientsCD57high cellswereassociatedwithundifferentiatedtumorcells acrossallstagesandtendedtobemorefrequentafterchemotherapy. Conclusion:StrongexpressionofCD57correlateswithaggressiveattributesofU-NB1andSK-N-BE(2)-Cneuroblastomacells andislinkedwithundifferentiatedneuroblastomacellsinpatients. Citation: Schlitter A-M, Dorneburg C, Barth TFE, Wahl J, Schulte JH, et al. (2012) CD57high Neuroblastoma Cells Have Aggressive Attributes Ex Situ and an UndifferentiatedPhenotypeinPatients.PLoSONE7(8):e42025.doi:10.1371/jo