Astrocyte-Specific Expression Patterns Associated with the PDGF-Induced Glioma Microenvironment 英文参考文献.docVIP

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Astrocyte-Specific Expression Patterns Associated with the PDGF-Induced Glioma Microenvironment 英文参考文献.doc

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Astrocyte-Specific Expression Patterns Associated with the PDGF-Induced Glioma Microenvironment 英文参考文献

Astrocyte-SpecificExpressionPatternsAssociatedwith thePDGF-InducedGliomaMicroenvironment AmandaM.Katz1,2,3,NdukaM.Amankulor2,3,4,KenPitter1,2,3,KarimHelmy2,3,MassimoSquatrito2,3 , EricC.Holland2,3,4 * 1Biochemistry,Cell,andMolecularBiologyProgram,WeillMedicalCollegeofCornellUniversity,NewYork,NewYork,UnitedStatesofAmerica,2DepartmentofCancer BiologyandGenetics,MemorialSloan-KetteringCancerCenter,NewYork,NewYork,UnitedStatesofAmerica,3BrainTumorCenter,MemorialSloan-KetteringCancer Center,NewYork,NewYork,UnitedStatesofAmerica,4DepartmentsofNeurosurgery,NeurologyandSurgery,MemorialSloan-KetteringCancerCenter,NewYork,New York,UnitedStatesofAmerica Abstract Background:Thetumormicroenvironmentcontainsnormal,non-neoplasticcellsthatmaycontributetotumorgrowthand maintenance.WithinPDGF-drivenmurinegliomas,tumor-associatedastrocytes(TAAs)arealargecomponentofthetumor microenvironment. The function of non-neoplastic astrocytes in the glioma microenvironment has not been fully elucidated;moreover,thedifferencesbetweentheseastrocytesandnormalastrocytesareunknown.Wethereforesought to identify genes and pathways that are increased in TAAs relative to normal astrocytes and also to determine whether expressionofthesegenescorrelateswithgliomabehavior. Methodology/PrincipalFindings:WecomparedthegeneexpressionprofilesofTAAstonormalastrocytesandfoundthe AntigenPresentationPathwaytobesignificantlyincreasedinTAAs.Wethenidentifiedagenesignatureforglioblastoma (GBM)TAAsandvalidatedtheexpressionofsomeofthosegeneswithinthetumor.WealsoshowthatTAAsarederived fromthenon-tumor,stromalenvironment,incontrasttotheOlig2+tumorcellsthatconstitutetheneoplasticelementsin ourmodel.Finally,wevalidatethisGBMTAAsignatureinpatientsandshowthataTAA-derivedgenesignaturepredicts survivalspecificallyinthehumanproneuralsubtypeofglioma. Conclusions/Significance:OurdataidentifiesuniquegeneexpressionpatternsbetweenpopulationsofTAAsandsuggests potentialrolesforstromalastrocyteswithinthegliomamicroenvironment.Weshowthatce