2024
Vascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumor
2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysisCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeIL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive miceLenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma
Tran T, Caulfield J, Zhang L, Schoenfeld D, Djureinovic D, Chiang V, Oria V, Weiss S, Olino K, Jilaveanu L, Kluger H. Lenvatinib or anti-VEGF in combination with anti-PD-1 differentially augments anti-tumor activity in melanoma. JCI Insight 2023, 8: e157347. PMID: 36821392, PMCID: PMC10132152, DOI: 10.1172/jci.insight.157347.Peer-Reviewed Original ResearchConceptsTumor microenvironmentAnti-VEGFCytokine/chemokine signalingCytokine/chemokine profilingBlood-brain barrier modelBlood vesselsLeukocyte transmigrationTumor-associated blood vesselsTumor-associated macrophagesIntratumoral blood vesselsAnti-angiogenesis effectAnti-tumor activityExtracranial diseasePlasmacytoid DCsImmune checkpointsPD-1Melanoma murine modelImmune infiltrationBBB modelChemokine profilingEndothelial stabilizationMurine modelLenvatinibCombined targetingMelanoma model
2022
Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes
Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify beta cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7: e156330. PMID: 35925682, PMCID: PMC9536276, DOI: 10.1172/jci.insight.156330.Peer-Reviewed Original ResearchConceptsCheckpoint inhibitorsΒ-cellsPD-1/PD-L1 pathwayT-lymphocyte antigen-4PD-1 blockadePD-L1 pathwayDeath ligand 1NOD mouse modelDevelopment of diabetesHuman β-cellsAutoimmune complicationsNOD miceΒ-cell populationDeath-1Diabetes mellitusImmune infiltratesInflammatory mediatorsPancreatic inflammationPD-L1Induced diabetesLymphocytic infiltrationInflammatory cytokinesAntigen-4Immune cellsT cellsInhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatment
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockade
2020
Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance
Avitan-Hersh E, Feng Y, Oknin Vaisman A, Abu Ahmad Y, Zohar Y, Zhang T, Lee JS, Lazar I, Sheikh Khalil S, Feiler Y, Kluger H, Kahana C, Brown K, Ruppin E, Ronai ZA, Orian A. Regulation of eIF2α by RNF4 Promotes Melanoma Tumorigenesis and Therapy Resistance. Journal Of Investigative Dermatology 2020, 140: 2466-2477. PMID: 32360601, PMCID: PMC8081033, DOI: 10.1016/j.jid.2020.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorDrug Resistance, NeoplasmEukaryotic Initiation Factor-2FemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMelanomaMiceMitogen-Activated Protein KinasesNuclear ProteinsOncogenesPrognosisProtein Kinase InhibitorsProtein StabilityProto-Oncogene Proteins B-rafSkinSkin NeoplasmsTranscription FactorsUbiquitinationXenograft Model Antitumor AssaysConceptsUbiquitin ligase RNF4Elongation factor alphaPatient-derived melanomasIntegrated stress responseTherapy resistancePositive feed-forward loopTranscription factor 4Feed-forward loopOncogenic translationMolecular machineryMajor clinical challengePhosphorylated eIF2αHallmark of melanomaXenograft mouse modelHomologous proteinsStress responseMAPK inhibitorProtein stabilizationMelanoma tumorigenesisTumorigenic propertiesPoor prognosisFactor alphaClinical challengeMouse modelRNF4
2019
PLEKHA5 regulates tumor growth in metastatic melanoma
Zhang H, Zhu H, Deng G, Zito CR, Oria VO, Rane CK, Zhang S, Weiss SA, Tran T, Adeniran A, Zhang F, Zhou J, Kluger Y, Bosenberg MW, Kluger HM, Jilaveanu LB. PLEKHA5 regulates tumor growth in metastatic melanoma. Cancer 2019, 126: 1016-1030. PMID: 31769872, PMCID: PMC7147081, DOI: 10.1002/cncr.32611.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsApoptosis Regulatory ProteinsBiomarkers, TumorBrain NeoplasmsCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMaleMelanomaMiceMice, NudeMiddle AgedPhosphatidylinositol 3-KinasesPrognosisProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesTumor Cells, CulturedXenograft Model Antitumor AssaysYoung AdultConceptsTumor growthDisseminated melanomaExtracranial melanoma metastasesPI3K/AKT/mTOR pathwayMelanoma brain metastasesBetter overall survivalPI3K/Akt/mTORAKT/mTOR pathwayCell proliferationAkt/mTORMelanoma xenograft modelGrowth of tumorsS cell cycle transitionBrain metastasesOverall survivalPoor prognosisMetastatic melanomaMAPK/ERKSubcutaneous inoculationMelanoma metastasesXenograft modelClinical relevanceMelanoma growthNude miceCerebral specimensB cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsB cell contentB-cell depletionAnti-tumor activityB cellsMuMT miceCell depletionAnti-PD-1 inhibitorsAnti-PD-1 responseB-cell depleting drugsTumor-infiltrating B cellsImpaired B-cell functionT cell-dependent tumor rejectionPD-1 inhibitionMC38 colon cancerB cell functionAnti-tumor effectsB-cell malignanciesMurine cancer modelsCell contentOverall survivalTumor rejectionCD20 antibodyAutoimmune disordersTumor shrinkageTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCells
2016
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathway
2015
The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation
Lau E, Feng Y, Claps G, Fukuda MN, Perlina A, Donn D, Jilaveanu L, Kluger H, Freeze HH, Ronai ZA. The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation. Science Signaling 2015, 8: ra124. PMID: 26645581, PMCID: PMC4818095, DOI: 10.1126/scisignal.aac6479.Peer-Reviewed Original ResearchConceptsProtein fucosylationFucose salvage pathwayTranscription factor ATF2Tumor microarray analysisProtein kinase CεTranscription factor 2Human melanoma specimensTranscriptional repressionPrimary melanoma growthPrimary melanocytesGenetic manipulationActive ATF2Cell motilityElucidation of mechanismsMicroarray analysisSalvage pathwayATF2Cell adhesionHigh abundanceCellular adhesionReduced motilityInvasive behaviorCell linesFactor 2Melanoma specimensRole of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis
Ma B, Herzog EL, Lee CG, Peng X, Lee CM, Chen X, Rockwell S, Koo JS, Kluger H, Herbst RS, Sznol M, Elias JA. Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis. Cancer Research 2015, 75: 487-496. PMID: 25511377, PMCID: PMC4321965, DOI: 10.1158/0008-5472.can-13-3339.Peer-Reviewed Original ResearchConceptsMelanoma lung metastasisPulmonary melanoma metastasesPulmonary metastasesLung metastasesMelanoma metastasesGenetic deletionBreast cancer cellsPlexin C1 receptorsPulmonary microenvironmentPoor prognosisSemaphorin 7AMelanoma spreadChitinase 3MetastasisCHI3L1Cancer progressionSema7AInhibitory wayCancer cellsReceptorsSignificant reductionΒ1 integrinNovel pathwayCritical roleIL13Rα2
2013
Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma
Scortegagna M, Ruller C, Feng Y, Lazova R, Kluger H, Li JL, De SK, Rickert R, Pellecchia M, Bosenberg M, Ronai ZA. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten–/– melanoma. Oncogene 2013, 33: 4330-4339. PMID: 24037523, PMCID: PMC3955742, DOI: 10.1038/onc.2013.383.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorForkhead Box Protein O3Forkhead Transcription FactorsGene Knockout TechniquesHumansIndazolesLung NeoplasmsLymphatic MetastasisMelanoma, ExperimentalMiceMice, KnockoutMutation, MissenseProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePyrimidinesPyruvate Dehydrogenase Acetyl-Transferring KinaseSignal TransductionSkin NeoplasmsTissue Array AnalysisConceptsPhosphoinositide-dependent kinase 1Protein kinase CAGC kinasesSerine/threonine protein kinasePDK1 expressionThreonine protein kinaseImportant cellular processesDirect genetic evidenceGene expression analysisActivity of AktCellular processesProtein kinaseGenetic evidenceExpression analysisPDK1 deletionKinase 1Kinase CElevated phosphorylationGenetic inactivationKinaseMelanoma invasionMelanoma developmentColony formationPharmacological inhibitionInhibits metastasis
2010
A Role for ATF2 in Regulating MITF and Melanoma Development
Shah M, Bhoumik A, Goel V, Dewing A, Breitwieser W, Kluger H, Krajewski S, Krajewska M, DeHart J, Lau E, Kallenberg DM, Jeong H, Eroshkin A, Bennett DC, Chin L, Bosenberg M, Jones N, Ronai ZA. A Role for ATF2 in Regulating MITF and Melanoma Development. PLOS Genetics 2010, 6: e1001258. PMID: 21203491, PMCID: PMC3009656, DOI: 10.1371/journal.pgen.1001258.Peer-Reviewed Original ResearchConceptsMelanoma developmentMouse melanoma modelHuman melanoma cell linesMITF expressionMelanoma tissue microarrayMelanoma cell linesMetastatic diseasePoor prognosisTissue microarrayXenograft modelMelanoma modelPrimary specimensPrimary human melanocytesOncogenic BRAFMiceGene expression profilingHigh MITF expressionDependent suppressionATF2 knockdownCell linesSoft agarHuman melanocytesMelanocytesMelanoma susceptibilityPrimary melanocytes
2008
Suppressor role of activating transcription factor 2 (ATF2) in skin cancer
Bhoumik A, Fichtman B, DeRossi C, Breitwieser W, Kluger HM, Davis S, Subtil A, Meltzer P, Krajewski S, Jones N, Ronai Z. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 1674-1679. PMID: 18227516, PMCID: PMC2234203, DOI: 10.1073/pnas.0706057105.Peer-Reviewed Original ResearchMeSH Keywords9,10-Dimethyl-1,2-benzanthraceneActivating Transcription Factor 2AnimalsApoptosisBeta CateninCarcinogensCell ProliferationCyclin D1DNAEpidermisKeratinocytesMiceMice, KnockoutPapillomaPresenilin-1Proto-Oncogene Proteins c-mybReceptor, Notch1Skin NeoplasmsTetradecanoylphorbol AcetateTissue Array AnalysisTumor Suppressor ProteinsConceptsSkin tumor formationTranscription factor 2Two-stage skin carcinogenesis protocolTumor formationBasal cell carcinomaSkin carcinogenesis protocolFactor 2K14-Cre miceCell carcinomaCarcinogenesis protocolMouse modelBeta-catenin expressionPapilloma developmentSkin cancerExhibit reduced expressionAnchorage-independent growthNormal skinNotch1 expressionCyclin D1MiceReduced expressionSuppressor roleSuppressor activitySelective expressionBasal layer
2006
Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification
Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R. Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification. Journal Of Investigative Dermatology 2006, 126: 2257-2271. PMID: 16810302, DOI: 10.1038/sj.jid.5700386.Peer-Reviewed Original ResearchConceptsX chromosome-linked geneSpecific gene expressionTranscription initiation siteSpecific promoter regionsMelanoma cellsGTPase mutantsEpigenetic modificationsSmall GTPaseDNA methylationVesicular transportRab33AGene expressionPromoter regionMelanosomal proteinsInitiation siteNormal melanocytesAberrant downregulationGenesEarly eventsAberrant processesMelanocytesExpressionGTPaseImportant roleNormal process
2005
Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease
Kluger HM, Lev D, Kluger Y, McCarthy MM, Kiriakova G, Camp RL, Rimm DL, Price JE. Using a Xenograft Model of Human Breast Cancer Metastasis to Find Genes Associated with Clinically Aggressive Disease. Cancer Research 2005, 65: 5578-5587. PMID: 15994930, DOI: 10.1158/0008-5472.can-05-0108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell AdhesionCell Growth ProcessesCell Line, TumorDisease Models, AnimalFemaleGene Expression ProfilingHumansImmunohistochemistryMiceMice, NudeMultivariate AnalysisNeoplasm InvasivenessNeoplasm MetastasisNeoplasm TransplantationOligonucleotide Array Sequence AnalysisPredictive Value of TestsReproducibility of ResultsTissue Array AnalysisTransplantation, HeterologousConceptsBreast cancerXenograft modelHuman breast cancer metastasisLymph node involvementLymph node metastasisChemokine ligand 1Human breast cancer cell linesBreast cancer metastasisLeukocyte protease inhibitorBreast cancer cell linesBreast cancer tissuesHSP-70 expressionHeat shock protein 70Cancer cell linesShock protein 70Identification of genesNode involvementNode metastasisAggressive diseaseClinicopathologic variablesPrimary tumorPrognostic markerNovel therapiesCDNA microarray analysisCancer tissues