2018
Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma
Cadamuro M, Brivio S, Mertens J, Vismara M, Moncsek A, Milani C, Fingas C, Cristina Malerba M, Nardo G, Dall'Olmo L, Milani E, Mariotti V, Stecca T, Massani M, Spirli C, Fiorotto R, Indraccolo S, Strazzabosco M, Fabris L. Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma. Journal Of Hepatology 2018, 70: 700-709. PMID: 30553841, PMCID: PMC10878126, DOI: 10.1016/j.jhep.2018.12.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCancer-Associated FibroblastsCell Line, TumorCholangiocarcinomaDisease Models, AnimalEndothelial CellsHeterograftsHumansImatinib MesylateLiverLymphangiogenesisLymphokinesMaleMiceMice, SCIDMyofibroblastsPlatelet-Derived Growth FactorProtein Kinase InhibitorsRatsRats, Inbred F344Receptor, Platelet-Derived Growth Factor betaVascular Endothelial Growth Factor AVascular Endothelial Growth Factor CConceptsCancer-associated fibroblastsLymphatic endothelial cellsCholangiocarcinoma specimensMetastatic spreadStromal reactionLiver myofibroblastsGrowth factorExtensive stromal reactionLymph node metastasisEarly metastatic spreadLevels of VEGFBH3 mimetic navitoclaxPlatelet-derived growth factorRole of PDGFVascular growth factorsTumor-associated lymphangiogenesisVEGF-C secretionTransendothelial electric resistanceCholangiocarcinoma invasivenessHuman lymphatic endothelial cellsCurative therapyNode metastasisBiliary treeEarly metastasisPDGFRβ inhibitor
2016
Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease
Spirli C, Mariotti V, Villani A, Fabris L, Fiorotto R, Strazzabosco M. Adenylyl cyclase 5 links changes in calcium homeostasis to cAMP-dependent cyst growth in polycystic liver disease. Journal Of Hepatology 2016, 66: 571-580. PMID: 27826057, PMCID: PMC5316496, DOI: 10.1016/j.jhep.2016.10.032.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl Cyclase InhibitorsAdenylyl CyclasesAnimalsCalciumCell ProliferationCyclic AMPCystsDisease Models, AnimalHomeostasisHumansLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutPolycystic Kidney, Autosomal DominantRNA InterferenceSignal TransductionStromal Interaction Molecule 1TRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsProgressive cyst growthPolycystic liver diseaseNovel therapeutic targetLiver diseaseKO miceCyst growthTherapeutic targetBiliary organoidsDouble conditional knockout miceCAMP productionAutosomal dominant polycystic kidney diseaseVascular endothelial growth factorCell proliferationDominant polycystic kidney diseaseEndothelial growth factorConditional knockout micePolycystic kidney diseaseLiver transplantationLevels of cAMPStore-operated CaCystic areasKidney diseaseCyst sizeVivo treatmentKnockout mice
2012
Altered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes
Spirli C, Locatelli L, Fiorotto R, Morell CM, Fabris L, Pozzan T, Strazzabosco M. Altered store operated calcium entry increases cyclic 3′,5′‐adenosine monophosphate production and extracellular signal‐regulated kinases 1 and 2 phosphorylation in polycystin‐2‐defective cholangiocytes. Hepatology 2012, 55: 856-868. PMID: 21987453, PMCID: PMC3272110, DOI: 10.1002/hep.24723.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsBile DuctsCalciumCalcium ChannelsCalcium SignalingCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesHomeostasisMembrane GlycoproteinsMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Models, AnimalPhosphorylationSignal TransductionStromal Interaction Molecule 1TRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsSensor stromal interaction molecule 1Adenylyl cyclase type 6Extracellular signal-regulated kinases 1Signal-regulated kinases 1Overproduction of cAMPStromal interaction molecule 1Orai channelsWild-type miceSOCE activationCAMP productionRapamycin (mTOR) signalingKinase 1ERK pathwayERK1/2 activationHuman diseasesWT cellsMammalian targetDependent activationSTIM-1CAMP/Inappropriate activationCyst growthCystic cholangiocytesPolycystic liver diseaseActivation
2009
Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver cyst growth in polycystin‐2–defective mice
Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, Tian X, Somlo S, Strazzabosco M. Mammalian target of rapamycin regulates vascular endothelial growth factor–dependent liver cyst growth in polycystin‐2–defective mice. Hepatology 2009, 51: 1778-1788. PMID: 20131403, PMCID: PMC2930014, DOI: 10.1002/hep.23511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCystsDisease Models, AnimalExtracellular Signal-Regulated MAP KinasesHypoxia-Inducible Factor 1, alpha SubunitInsulin-Like Growth Factor IIntracellular Signaling Peptides and ProteinsLiver DiseasesMicePolycystic Kidney, Autosomal DominantProtein Serine-Threonine KinasesSirolimusTOR Serine-Threonine KinasesTRPP Cation ChannelsVascular Endothelial Growth Factor AConceptsMammalian targetInsulin-like growth factor-1Extracellular signal-regulated kinase 1/2Extracellular signal-regulated kinaseSignal-regulated kinase 1/2Autosomal dominant polycystic kidney diseaseLiver cyst growthVascular endothelial growth factorProtein kinase AInsulin-like growth factor 1 receptorSignal-regulated kinaseGrowth factor 1 receptorVEGF secretionCyst growthMTOR inhibitor rapamycinFactor 1 receptorHIF1alpha accumulationFactor 1 alphaDependent phosphorylationKinase AKinase 1/2P-P70S6KInhibitor rapamycinHypoxia-inducible factor-1 alphaExpression of CC3ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice
Spirli C, Okolicsanyi S, Fiorotto R, Fabris L, Cadamuro M, Lecchi S, Tian X, Somlo S, Strazzabosco M. ERK1/2-Dependent Vascular Endothelial Growth Factor Signaling Sustains Cyst Growth in Polycystin-2 Defective Mice. Gastroenterology 2009, 138: 360-371.e7. PMID: 19766642, PMCID: PMC3000794, DOI: 10.1053/j.gastro.2009.09.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCyclic AMP-Dependent Protein KinasesCystsHypoxia-Inducible Factor 1, alpha SubunitIndolesLiver DiseasesMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhenotypePhosphorylationProliferating Cell Nuclear AntigenProtein Kinase InhibitorsPyrrolesRepressor ProteinsTRPP Cation ChannelsTumor Suppressor ProteinsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVascular endothelial growth factorPolycystic liver diseaseVEGF secretionLiver cystsLiver diseaseVEGFR-2Cyst growthLiver/body weight ratioAdult dominant polycystic kidney diseaseParacrine vascular endothelial growth factorSecretion of VEGFHIF-1alphaBody weight ratioEffects of VEGFAutocrine vascular endothelial growth factorDominant polycystic kidney diseaseExpression of pERKVascular endothelial growth factor signalingPhosphorylated VEGFR-2Liver cyst growthEndothelial growth factorPolycystic kidney diseaseCyst epithelial cellsExtracellular signal-regulated kinase 1/2Hypoxia-inducible factor
2006
Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases
Fabris L, Cadamuro M, Fiorotto R, Roskams T, Spirlì C, Melero S, Sonzogni A, Joplin RE, Okolicsanyi L, Strazzabosco M. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology 2006, 43: 1001-1012. PMID: 16628643, DOI: 10.1002/hep.21143.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenic ProteinsAnimalsBile DuctsCystsHumansImmunohistochemistryLiver DiseasesMicePolycystic Kidney, Autosomal DominantVascular Endothelial Growth Factor AConceptsAutosomal dominant polycystic kidney diseaseVascular endothelial growth factorPolycystic liver diseaseAng-1Liver diseaseDuctal platePortal vasculatureAng-2 gene expressionTie-2Expression of VEGFEmbryonic ductal plateDuctal plate cellsEffects of VEGFDominant polycystic kidney diseaseLiver cyst growthEndothelial growth factorAutocrine proliferative effectsPolycystic kidney diseaseLiver involvementADPKD mouse modelBiliary cystsCaroli's diseaseKidney diseaseADPKD patientsAng-2