Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression 英文参考文献.docVIP

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Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression 英文参考文献.doc

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Mesenchymal Stem Cell Transition to Tumor-Associated Fibroblasts Contributes to Fibrovascular Network Expansion and Tumor Progression 英文参考文献

MesenchymalStemCellTransitiontoTumor-Associated FibroblastsContributestoFibrovascularNetwork ExpansionandTumorProgression ErikaL.Spaeth1.,JenniferL.Dembinski1.¤,A.KateSasser2,KeriWatson1,AnnKlopp1,BrettHall2, MichaelAndreeff1,FrankMarini1* 1SectionofMolecularHematologyandTherapy,DepartmentofStemCellTransplantationandCellularTherapy,TheUniversityofTexasM.D.AndersonCancerCenter, Houston,Texas,UnitedStatesofAmerica,2DepartmentofPediatrics,TheOhioStateUniversityandCenterforChildhoodCancer,ColumbusChildren’sResearchInstitute, Columbus,Ohio,UnitedStatesofAmerica Abstract Background: Tumor associated fibroblasts (TAF), are essential for tumor progression providing both a functional and structural supportive environment. TAF, known as activated fibroblasts, have an established biological impact on tumorigenesisasmatrixsynthesizingormatrixdegradingcells,contractilecells,andevenbloodvesselassociatedcells.The productionofgrowthfactors,cytokines,chemokines,matrix-degradingenzymes,andimmunomodulatorymechanismsby thesecellsaugmenttumorprogressionbyprovidingasuitableenvironment.ThereareseveralsuggestedoriginsoftheTAF includingtissue-resident,circulating,andepithelial-to-mesenchymal-transitionedcells. Methodology/Principal Findings: We provide evidence that TAF are derived from mesenchymal stem cells (MSC) that acquireaTAFphenotypefollowingexposuretoorsystemicrecruitmentintoadenocarcinomaxenograftmodelsincluding breast, pancreatic, and ovarian. We define the MSC derived TAF in a xenograft ovarian carcinoma model by the immunohistochemicalpresenceof1)fibroblastspecificproteinandfibroblastactivatedprotein;2)markersphenotypically associated with aggressiveness, including tenascin-c, thrombospondin-1, and stromelysin-1; 3) production of pro- tumorigenicgrowthfactorsincludinghepatocytegrowthfactor,epidermalgrowthfactor,andinterleukin-6;and4)factors indicative of vascularization, including alpha-smooth muscle actin, desmin, and vascular endothelial growth factor. We demonstratethatund