Search results for " Osteonectin"

showing 5 items of 5 documents

Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities

2017

JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino acid sequences of JMJD6 necessary for the interaction with Coll-I ar…

0301 basic medicineMonoclonal antibodyXenograft Model Antitumor AssayArginineLysyl hydroxylaseEnzyme-Linked Immunosorbent AssayReceptors Cell SurfacePlasma protein bindingBiochemistryCollagen Type IExtracellular matrix03 medical and health sciencesMiceFibrosisPeptide LibraryCell Line TumormedicineGeneticsAnimalsHumansOsteonectinCell NucleuMolecular BiologyCell NucleusMice KnockoutMice Inbred BALB CbiologyChemistryJmjC familyAnimalAntibodies MonoclonalFibrillogenesisExtracellular matrixmedicine.diseaseXenograft Model Antitumor AssaysImmunohistochemistryCell biologyIn vivo treatment030104 developmental biologybiology.proteinOsteonectinSignal transductionExtracellular matrix; In vivo treatment; JmjC family; Monoclonal antibody; Peptide library; Animals; Antibodies Monoclonal; Cell Line Tumor; Cell Nucleus; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Humans; Immunohistochemistry; Mice; Mice Inbred BALB C; Mice Knockout; Osteonectin; Peptide Library; Protein Binding; Receptors Cell Surface; Signal Transduction; Xenograft Model Antitumor Assays; Biotechnology; Biochemistry; Molecular Biology; GeneticsHumanProtein BindingSignal TransductionBiotechnology
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SCD5-induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B

2014

A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl-CoA desaturase SCD5 in converting saturated FAs into mono-unsaturated FAs during melanoma progression. SCD5 is down-regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPAR…

cathepsin B2734Intracellular SpaceDown-RegulationCell LineMelanocyteCell Line TumormelanomaHumansintracellular acidityOsteonectinNeoplasticTumorMedicine (all)Fatty AcidsSPARCHydrogen-Ion ConcentrationGene Expression Regulation NeoplasticSCD5Gene Expression Regulationoleic acidDisease ProgressionMelanocytesFatty AcidStearoyl-CoA Desaturasecathepsin B; intracellular acidity; melanoma; oleic acid; SCD5; SPARC; Cathepsin B; Cell Line Tumor; Disease Progression; Down-Regulation; Fatty Acids; Humans; Hydrogen-Ion Concentration; Intracellular Space; Melanocytes; Melanoma; Oleic Acid; Osteonectin; Stearoyl-CoA Desaturase; Gene Expression Regulation Neoplastic; 2734; Medicine (all)Human
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Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.

2021

Abstract Fatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablis…

MaleCancer ResearchStromal cellAnimals Biomarkers Tumor Cell Differentiation Cell Line Tumor Coculture Techniques Endoplasmic Reticulum Chaperone BiP Epigenesis Genetic Gene Expression Regulation Neoplastic Humans Male Mice Mice Inbred C57BL Neuroendocrine Cells Osteonectin Prostatic Neoplasms Stromal Cells Transgenes Tumor Microenvironment Down-RegulationDown-RegulationContext (language use)Settore MED/08 - Anatomia PatologicaNeuroendocrine differentiationEpigenesis GeneticProstate cancerMiceStromaDownregulation and upregulationNeuroendocrine CellsCell Line TumormedicineBiomarkers TumorTumor MicroenvironmentSettore MED/05 - Patologia ClinicaAnimalsHumansOsteonectinEpigeneticsTransgenesEndoplasmic Reticulum Chaperone BiPbusiness.industryMatricellular proteinProstatic NeoplasmsCell Differentiationmedicine.diseaseCoculture TechniquesGene Expression Regulation NeoplasticMice Inbred C57BLOncologyCancer researchStromal CellsbusinessCancer research
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Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma

2013

Abstract Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5+ B cells, which underwent malignant …

MyeloidLymphoid Tissue: immunologyLymphomaNeutrophilsChronic lymphocytic leukemiaAutoimmunityOsteonectin: geneticsCHRONIC LYMPHOCYTIC-LEUKEMIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INHIBITORY RECEPTOR LAIR-1; KAPPA-B ACTIVATION; MARGINAL ZONE; INFLAMMATORY DISORDERS; MATRICELLULAR PROTEIN; SPARCMalignant transformationExtracellular matrixKAPPA-B ACTIVATIONLymphoma: immunologyMicehemic and lymphatic diseasesOsteonectinSYSTEMIC-LUPUS-ERYTHEMATOSUSNF-kappa B: immunologyCells CulturedTissue homeostasisB-LymphocytesCulturedNF-kappa BLymphoid Tissue: cytologyCell biologyCD5: immunologyExtracellular MatrixMutant Strainsmedicine.anatomical_structureINHIBITORY RECEPTOR LAIR-1OncologyCD95Stromal cellLymphoid TissueCellsBiologyCD95: geneticsCD5 AntigensINFLAMMATORY DISORDERSExtracellular Matrix: immunologymedicineAnimalsHumansfas ReceptorAntigensB-Lymphocytes: immunologyMATRICELLULAR PROTEINCHRONIC LYMPHOCYTIC-LEUKEMIASPARCLymphoma: geneticsNeutrophil extracellular trapsmedicine.diseaseAnimals; Antigens; Autoimmunity; B-Lymphocytes; B-Lymphocytes: immunology; CD5; CD5: immunology; CD95; CD95: genetics; Cells; Cultured; Extracellular Matrix; Extracellular Matrix: immunology; Humans; Lymphoid Tissue; Lymphoid Tissue: cytology; Lymphoid Tissue: immunology; Lymphoma; Lymphoma: genetics; Lymphoma: immunology; Mice; Mutant Strains; NF-kappa B; NF-kappa B: immunology; Neutrophils; Neutrophils: immunology; Osteonectin; Osteonectin: genetics; Osteonectin: immunologyMice Mutant StrainsCD5Neutrophils: immunologyOsteonectin: immunologyMARGINAL ZONELymphoma SPARC autoimmunityCD5
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SPARC oppositely regulates inflammation and fibrosis in bleomycin-induced lung damage.

2011

Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) >WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sparc(-/-) macrophages to down-regulate tumor necrosis …

Pathologymedicine.medical_specialtyAnimals; Bleomycin; Bone Marrow Cells; Chimera; Collagen; Down-Regulation; Fibroblasts; Leukocytes; Macrophages; Mice; Mice Inbred BALB C; Osteonectin; Pneumonia; Pulmonary Fibrosis; Transforming Growth Factor beta; Tumor Necrosis Factor-alphaPulmonary FibrosisDown-RegulationInflammationBone Marrow CellsBiologyPathology and Forensic MedicineMiceFibrosisTumor necrosis factor productionTransforming Growth Factor betaPulmonary fibrosismedicineLeukocytesAnimalsOsteonectinInbred BALB CChimeraTumor Necrosis Factor-alphaMacrophagesMatricellular proteinRegular ArticleSPARCTransforming growth factor betaPneumoniaFibroblastsBLEOMYCINmedicine.diseaseSPARC; BLEOMYCIN; LUNG DAMAGELUNG DAMAGECancer researchbiology.proteinTumor necrosis factor alphaCollagenmedicine.symptomOsteonectin
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