Senescent Cells in Growing Tumors Population Dynamics and Cancer Stem Cells 英文参考文献.docVIP

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Senescent Cells in Growing Tumors Population Dynamics and Cancer Stem Cells 英文参考文献.doc

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Senescent Cells in Growing Tumors Population Dynamics and Cancer Stem Cells 英文参考文献

SenescentCellsinGrowingTumors:Population DynamicsandCancerStemCells CaterinaA.M.LaPorta1,StefanoZapperi2,3*,JamesP.Sethna4 1DepartmentofBiomolecularScienceandBiotechnology,UniversityofMilano,Milano,Italy,2CNR-IENI,Milano,Italy,3ISIFoundation,Torino,Italy,4LASSP,Department ofPhysics,CornellUniversity,Ithaca,NewYork,UnitedStatesofAmerica Abstract Tumorsaredefinedbytheirintenseproliferation,butsometimescancercellsturnsenescentandstopreplicating.Inthe stochasticcancermodelinwhichallcellsaretumorigenic,senescenceisseenastheresultofrandommutations,suggesting thatitcouldrepresentabarriertotumorgrowth.Inthehierarchicalcancermodelasubsetofthecells,thecancerstemcells, divideindefinitelywhileothercellseventuallyturnsenescent.Hereweformulatecancergrowthinmathematicaltermsand obtain predictions for the evolution of senescence. We perform experiments in human melanoma cells which are compatible with the hierarchical model and show that senescence is a reversible process controlled by survivin. We concludethatenhancingsenescenceisunlikelytoprovideausefultherapeuticstrategytofightcancer,unlessthecancer stemcellsarespecificallytargeted. Citation:LaPortaCAM,ZapperiS,SethnaJP(2012)SenescentCellsinGrowingTumors:PopulationDynamicsandCancerStemCells.PLoSComputBiol8(1): e1002316.doi:10.1371/journal.pcbi.1002316 Editor:EytanDomany,WeizmannInstituteofScience,Israel ReceivedJuly25,2011;AcceptedNovember2,2011;PublishedJanuary19,2012 Copyright: ? 2012 La Porta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: JPS acknowledges NCI-U54CA143876 for support. CAMLP is supported by PRIN 2008BP25KN004. The funders had no role in study design, data collectionandanalysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:stefano.zapperi@cnr.