2018
Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2
Incio J, Ligibel JA, McManus DT, Suboj P, Jung K, Kawaguchi K, Pinter M, Babykutty S, Chin SM, Vardam TD, Huang Y, Rahbari NN, Roberge S, Wang D, Gomes-Santos IL, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Tolaney SM, Krop IE, Duda DG, Boucher Y, Fukumura D, Jain RK. Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. Science Translational Medicine 2018, 10 PMID: 29540614, PMCID: PMC5936748, DOI: 10.1126/scitranslmed.aag0945.Peer-Reviewed Original ResearchConceptsVEGF therapyInterleukin-6Breast cancerMouse modelAnti-vascular endothelial growth factor therapyEndothelial growth factor therapyTumor vasculatureAnti-VEGF therapyAnti-VEGF treatmentIL-6 blockadeGrowth factor therapyIL-6 productionFGF-2Up-regulates IL-6Second mouse modelFGF-2 expressionTumor cell proliferationFactor therapyGrowth factor 2Proinflammatory factorsMetastatic sitesBC patientsObese miceReceptor inhibitionSystemic concentrations
2016
PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity
Incio J, Tam J, Rahbari NN, Suboj P, McManus DT, Chin SM, Vardam TD, Batista A, Babykutty S, Jung K, Khachatryan A, Hato T, Ligibel JA, Krop IE, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Shibuya M, Carmeliet P, Soares R, Duda DG, Jain RK, Fukumura D. PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity. Clinical Cancer Research 2016, 22: 2993-3004. PMID: 26861455, PMCID: PMC4911258, DOI: 10.1158/1078-0432.ccr-15-1839.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsDiet, High-FatFemaleGlucoseHumansHypoglycemic AgentsMacrophagesMetforminMiceMice, Inbred C57BLMice, KnockoutMice, ObeseNeovascularization, PathologicObesityPancreatic NeoplasmsPlacenta Growth FactorPrognosisSignal TransductionVascular Endothelial Growth Factor Receptor-1ConceptsMouse modelTumor progressionTumor-associated macrophage recruitmentDiet-induced obese mouse modelTumor angiogenesisVEGFR-1Breast cancer mouse modelRole of PlGFBreast cancer patientsTumor immune microenvironmentObese mouse modelPlacental growth factorWild-type C57BL/6Addition of metforminHigh-fat dietTumor immune environmentCancer mouse modelReceptors VEGFR-1Breast cancer modelBreast cancer progressionAntitumor immunityTAM infiltrationImmune environmentInsulin levelsImmune microenvironment