Disseminated Breast Cancer Cells Acquire a Highly Malignant and Aggressive Metastatic Phenotype during Metastatic Latency in the Bone 英文参考文献.docVIP
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Disseminated Breast Cancer Cells Acquire a Highly Malignant and Aggressive Metastatic Phenotype during Metastatic Latency in the Bone 英文参考文献
DisseminatedBreastCancerCellsAcquireaHighly
MalignantandAggressiveMetastaticPhenotypeduring
MetastaticLatencyintheBone
CarolynG.Marsden1,MaryJoWright2,LatonyaCarrier1,KrzysztofMoroz3,BrianG.Rowan1*
1DepartmentofStructuralandCellularBiology,TheLouisianaCancerResearchConsortium,TulaneUniversityHealthSciencesCenter,NewOrleans,Louisiana,United
StatesofAmerica,2DepartmentofSurgery,TheLouisianaCancerResearchConsortium,TulaneUniversitySchoolofMedicine,NewOrleans,Louisiana,UnitedStatesof
America,3SectionofSurgicalPathologyandCytopathology,LouisianaCancerResearchConsortium,TulaneUniversitySchoolofMedicine,NewOrleans,Louisiana,United
StatesofAmerica
Abstract
Background:Disseminatedtumorcells(DTCs)inthebonemarrowmayexistinadormantstateforextendedperiodsof
time,maintainingtheabilitytoproliferateuponactivation,engraftatnewsites,andformdetectablemetastases.However,
understandingofthebehaviorandbiologyofdormantbreastcancercellsinthebonemarrownicheremainslimited,aswell
astheirpotentialinvolvementintumorrecurrenceandmetastasis.Therefore,thepurposeofthisstudywastoinvestigate
thetumorigenicityandmetastaticpotentialofdormantdisseminatedbreastcancercells(priortoactivation)inthebone
marrow.
Methodology/PrincipalFindings:Totalbonemarrow,isolatedfrommicepreviouslyinjectedwithtumorspheresintothe
mammaryfatpad,wasinjectedintothemammaryfatpadofNUDEmice.Asanegativecontrol,bonemarrowisolatedfrom
non-injected mice was injected into the mammary fat pad of NUDE mice. The resultant tumors were analyzed by
immunohistochemistry for expression of epithelial and mesenchymal markers. Mouse lungs, livers, and kidneys were
analyzedbyH+Estainingtodetectmetastases.Theinjectionofbonemarrowisolatedfrommicepreviouslyinjectedwith
tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post-
injection.However,theinjectionofbonemarrowisolatedfromnon-injectedmicedidnotresultintumorformationinthe
mammaryfatpad.TheDTC-derivedtumorsexhibitedaccelerateddevelopmentofme
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