Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism 英文参考文献.docVIP

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Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism 英文参考文献.doc

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Differential Matrix Rigidity Response in Breast Cancer Cell Lines Correlates with the Tissue Tropism 英文参考文献

DifferentialMatrixRigidityResponseinBreastCancer CellLinesCorrelateswiththeTissueTropism AnaKostic,ChristopherD.Lynch,MichaelP.Sheetz* DepartmentofBiologicalSciences,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Metastasistoavarietyofdistantorgans,suchaslung,brain,bone,andliver,isaleadingcauseofmortalityinthebreast cancerpatients.Thetissuetropismofbreastcancermetastasishasbeenrecognizedandstudiedextensively,butthecellular processesunderlyingthisphenomenon,remainelusive.Moderntechnologieshaveenabledthediscoveryofanumberof thegeneticfactorsdeterminingtissuetropismofmalignantcells.However,theeffectofthesegeneticdifferencesonthe cellmotilityandinvasivenessispoorlyunderstood.Here,wereportthatcellularresponsestothemechanicalrigidityofthe extracellularmatrixcorrelatewiththerigidityofthetargettissue.Wetestedaseriesofsinglecellpopulationsisolatedfrom MDA-MB-231breastcancercelllineinavarietyofassayswheretheextracellularmatrixrigiditywasvaried tomimicthe environmentthatthesecellsmightencounterinvivo.Therewasincreasedproliferationandmigrationthroughthematrices ofrigiditiescorrespondingtothenativerigiditiesoftheorganswheremetastasiswasobserved.Wewereabletoabolishthe differentialmatrixrigidityresponsebyknockingdownFynkinase,whichwaspreviouslyidentifiedasacriticalcomponentof the FN rigidity response pathway in healthy cells. This result suggests possible molecular mechanisms of the rigidity responseinthemalignantcells,indicatingpotentialcandidatesfortherapeuticinterventions. Citation:KosticA,LynchCD,SheetzMP(2009)DifferentialMatrixRigidityResponseinBreastCancerCellLinesCorrelateswiththeTissueTropism.PLoSONE4(7): e6361.doi:10.1371/journal.pone.0006361 Editor:SyedA.Aziz,HealthCanada,Canada ReceivedMarch4,2009;AcceptedMay27,2009;PublishedJuly23,2009 Copyright: ? 2009 Kostic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,p