Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression 英文参考文献.docVIP

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Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression 英文参考文献.doc

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ShigellaMediatedDepletionofMacrophagesinaMurine BreastCancerModelIsAssociatedwithTumor Regression KatharinaGalmbacher1.¤a,MartinHeisig1,2.,ChristianHotz1¤b,JoergWischhusen3 ,Antoine Galmiche1¤c,BirgitBergmann1,2,IvayloGentschev1¤d,WernerGoebel2¤e,UlfR.Rapp1¤f ,Joachim Fensterle1*¤g 1Institutfu¨rMedizinischeStrahlenkundeundZellforschung,Universita¨t Wu¨rzburg,Wu¨rzburg,Germany,2Institutfu¨rMikrobiologie,Biozentrum,Universita¨t Wu¨rzburg, Wu¨rzburg,Germany,3Universita¨tsfrauenklinik Wu¨rzburg,Wu¨rzburg,Germany Abstract Atumorpromotingroleofmacrophageshasbeendescribedforatransgenicmurinebreastcancermodel.Inthismodel tumor-associated macrophages (TAMs) represent a major component of the leukocytic infiltrate and areassociated with tumorprogression.Shigellaflexneriisabacterialpathogenknowntospecificlyinduceapotosisinmacrophages.Toevaluate whetherShigella-inducedremovalofmacrophagesmaybesufficientforachievingtumorregressionwehavedevelopedan attenuated strain of S. flexneri (M90TDaroA) and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenicmice.Quantitativeanalysisofbacterialtumortargetingdemonstratedthatattenuated,invasiveShigellaflexneri primarily infectedTAMsaftersystemic administration.Asinglei.v.injectionofinvasive M90TDaroAresulted incaspase-1 dependentapoptosisofTAMsfollowedbya74%reductionintumorsoftransgenicMMTV-HER-2mice7dayspostinfection. TAMdepletionwassustainedandassociatedwithcompletetumorregression. ThesedatasupportTAMsasusefultargets forantitumortherapyandhighlightattenuatedbacterialpathogensaspotentialtools. Citation:GalmbacherK,HeisigM,HotzC,WischhusenJ,GalmicheA,etal.(2010)ShigellaMediatedDepletionofMacrophagesinaMurineBreastCancerModelIs AssociatedwithTumorRegression.PLoSONE5(3):e9572.doi:10.1371/journal.pone.0009572 Editor:GeorgHa¨cker, TechnicalUniversityMunich,Germany ReceivedOctober30,2009;AcceptedFebr