GPMDB00235OtherDuhamel M, et al.InstrumentNot AvailableNot availableMus_musculus_viruses, Rabbit_calicivirus_australia_1_mic_07_uid33267, Rattus_norvegicus_papillomavirus_1_ees_2009_uid40233, Rat_coronavirus_parker_uid39313, Ratmichel.salzet@univ-lille1.fr26330543http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023540http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023550http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023546http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023535http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023545http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023534http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023537http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023548http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023536http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023542http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023541http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023544http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023533http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023543http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023539http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023549http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023538Inserm U-1192, France, et al.Not availableGPMDBMacrophages provide the first line of host immune defense. Their activation triggers the secretion of pro-inflammatory cytokines and chemokines recruiting other immune cells. In cancer, macrophages present an M2 anti-inflammatory phenotype promoting tumor growth. In this way, strategies need to be develop to reactivate macrophages. Previously thought to be expressed only in cells with a neural/neuroendocrine phenotype, the proprotein convertase 1/3 has been shown to also be expressed in macrophages and regulated as a function of the Toll-like receptor immune response. Here, we investigated the intracellular impact of the down-regulation of the proprotein convertase 1/3 in NR8383 macrophages and confirmed the results on macrophages from PC1/3 deficient mice. A complete proteomic study of secretomes and intracellular proteins was undertaken and revealed that inhibition of proprotein convertase 1/3 orient macrophages toward an M1 activated phenotype. This phenotype is characterized by filopodial extensions, Toll-like receptor 4 MyD88-dependent signaling, calcium entry augmentation and the secretion of pro-inflammatory factors. In response to endotoxin/lipopolysaccharide, these intracellular modifications increased, and the secreted factors attracted naïve T helper lymphocytes to promote the cytotoxic response. Importantly, the application of these factors onto breast and ovarian cancer cells resulted in a decrease viability or resistance. Under inhibitory conditions using interleukin 10, PC1/3-knockdown macrophages continued to secrete inflammatory factors. These data indicate that targeted inhibition of proprotein convertase 1/3 could represent a novel type of immune therapy to reactivate intra-tumoral macrophages.Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study.Duhamel Marie M,Rodet Franck F,Delhem Nadira N,Vanden Abeele Fabien F,Kobeissy Firas F,Nataf Serge S,Pays Laurent L,Desjardins Roxanne R,Gagnon Hugo H,Wisztorski Maxence M,Fournier Isabelle I,Day Robert R,Salzet Michel M,Duhamel Marie M, Rodet Franck F, Delhem Nadira N, Vanden Abeele Fabien F, Kobeissy Firas F, Nataf Serge S, Pays Laurent L, Desjardins Roxanne R, Gagnon Hugo H, Wisztorski Maxence M, Fournier Isabelle I, Day Robert R, Salzet Michel MProprotein Convertase SPC3, Prohormone Convertase, PC1 Prohormone Convertase, Monocyte Derived Macrophages, Convertase 1, Macrophages, Convertase PC1, Prohormone Convertase 3, PC1 Prohormone, study., Prohormone Convertase 1, Bone Marrow Derived Macrophages, Bone Marrow-Derived Macrophage, Monocyte Derived, Convertase, Neuroendocrine Convertase PC1, PC1, Proinsulin Convertase 1, Endoprotease, PC3, Bone Marrow-Derived, Neuroendocrine, Monocyte-Derived, PC3 Prohormone Convertase, Monocyte-Derived Macrophage, Bone Marrow-Derived Macrophages, Proprotein, PC3 Endoprotease, Convertase SPC3, PC1 Endoprotease, PC3 Prohormone, Monocyte-Derived Macrophages, MacrophageProhormone Convertase, data, nucleocytoplasm, PLXN5, mol, Monocyte Derived Macrophages, Convertase 1, Proteins, Phenotypes., Nl1, PC1 Prohormone, Gene, PLEXIN-B1, Mell1, Monocyte Derived, Convertase, Downregulation, Cell, Down Regulation, Neuroendocrine Convertase PC1, SeP, PC1, PC3, polypeptide, Neuroendocrine, Monocyte-Derived, Down-Regulation, CEH, Receptor Down-Regulation, MMEL2, PC3 Prohormone Convertase, Down-Regulation (Physiology), Protein, Monocyte-Derived Macrophage, Gene Products, NEPII, NL1, Convertase SPC3, NL2, SEH, internal to cell, Monocyte-Derived Macrophages, SEP, Macrophage, protoplasm, Proprotein Convertase SPC3, study, PC1 Prohormone Convertase, protoplast, cell, Macrophages, NR8383, Convertase PC1, Prohormone Convertase 3, Prohormone Convertase 1, Bone Marrow Derived Macrophages, Bone Marrow-Derived Macrophage, proteins, sEP, Proinsulin Convertase 1, Protein Gene Products, Endoprotease, Bone Marrow-Derived, Gene Proteins, Bone Marrow-Derived Macrophages, SELP, Proprotein, PC3 Endoprotease, Eph2, PC1 Endoprotease, Receptor, E430016J11Rik, PC3 Prohormone, RWDD5, NEP2Prohormone Convertase, Monocyte Derived Macrophages, Convertase 1, PKD1, K1CP, PC1 Prohormone, CK16, Monocyte Derived, Convertase, Neuroendocrine Convertase PC1, PC1, PBP, PC3, Neuroendocrine, Monocyte-Derived, PKD, PC3 Prohormone Convertase, Prkcm, Monocyte-Derived Macrophage, K16, Convertase SPC3, TRPP1, Monocyte-Derived Macrophages, Macrophage, Npps, Proprotein Convertase SPC3, PC1 Prohormone Convertase, mFLJ00285, Macrophages, Convertase PC1, Prohormone Convertase 3, Pc-1, study., Prohormone Convertase 1, Bone Marrow Derived Macrophages, Bone Marrow-Derived Macrophage, NEPPK, Proinsulin Convertase 1, Pkcm, Endoprotease, Bone Marrow-Derived, KRT16A, Bone Marrow-Derived Macrophages, FNEPPK, Proprotein, PC3 Endoprotease, PC1 Endoprotease, PC3 Prohormone, Pc1host organism, Breasts, nucleocytoplasm, Laboratory, Calcium 40, Mus domesticus, K1CP, Receptors, A4, response to LPS, CASP-14, Tumor, PPS1, Downregulation, House Mouse, Neuroendocrine Convertase PC1, hToll, lymphocytes, responsivity, Monocyte-Derived Macrophage, Prkcm, Convertase SPC3, TRPP1, treatment, calcio, Toll Like Receptor, increased, OVARY NEOPL, MYD88D, mFLJ00285, OFC6, Convertase PC1, PPS, Swiss Mice, present in organism, proteins, Toll Like Receptors, NEOPL OVARIAN, Endoprotease, signaling process, disease management, PC3 Endoprotease, Lymphoid, Ovarian Cancers, single organism signaling, Blood Coagulation Factor IV, Ca, Tumors, Pc1, mamma, Cancer of Ovary, Coagulation, external secretion, mouse, CK16, Toll-Like Receptor, VWS1, Convertase, tumours, results, PC1, PBP, PC3, exocrine gland fluid/secretion, Toll Like Receptor 4, Receptor Down-Regulation, Mini-ICE, Intercrines, secretion, Lymphoid Cell, internal to cell, activation, TLR4, Monocyte-Derived Macrophages, Ovary Neoplasm, Mus musculus, Interleukin, Caspase-14 subunit p10, growth pattern, non-developmental growth, mice, Toll-4 Receptor, Swiss Mouse, Pc-1, Caspase-14 subunit p19, Ovary Neoplasms, MICE, domesticus, Phenotypes, DMDA, Cells, Mouse, E430016J11Rik, exocrine gland secretion, accessory, Ovary Cancer, 3.4.22.-, mammary region, biological signaling, Chemotactic, exocrine gland fluid, Monocyte Derived Macrophages, exocrine gland fluid or secretion, Chemotactic Cytokines, Neoplasms, Gene, mini-ICE, supernumerary, TYPE, NEOPL, DAGA4, Bone Marrow-Derived Macrophages., OVARIAN NEOPL, Neuroendocrine, PC3 Prohormone Convertase, House, Ovarian, 20Ca, Factor IV, resistance, fam:TLR, Gene Products, Mus musculus domesticus, Toll Like, MAM, Mice, SCG3, malignant tumour, TLR4 Receptor, protoplasm, Npps, study, reactivity, Calcium-40, protoplast, response to endotoxin, Swiss, NR8383, Lps, LPS, Ovarian Cancer, mammary part of chest, Prohormone Convertase 3, malignant neoplasia, Prohormone Convertase 1, Bone Marrow-Derived Macrophage, tumour, NEPPK, Proinsulin Convertase 1, Bone Marrow-Derived, CD284, secreted substance, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), lipopolysaccharides, bodily secretion, KRT16A, FNEPPK, PC1 Endoprotease, PIT, Neoplastic Growth, Lymphocyte, Cancer, Prohormone Convertase, data, Malignant Neoplasm, Convertase 1, PKD1, Proteins, Ovary, PC1 Prohormone, Monocyte Derived, function, Kalzium, Ovary Cancers, Cell, Down Regulation, LGMD2C, polypeptide, Cytokines, Monocyte-Derived, Down-Regulation, PKD, Mus, Down-Regulation (Physiology), Protein, Neoplasm, K16, VWS, Toll 4 Receptor, Lymphoid Cells, Macrophage, Proprotein Convertase SPC3, Cancer of the Ovary, Calcium, PC1 Prohormone Convertase, Toll-Like, DMDA1, Macrophages, increased number, OC, Bone Marrow Derived Macrophages, House Mice, Cancers, Ovarian Neoplasms, malignant tumor, signalling, Laboratory Mice, Pkcm, Protein Gene Products, Gene Proteins, present in greater numbers in organism, Coagulation Factor IV, signalling process, Ovarian Neoplasm, SCARMD2, Bone Marrow-Derived Macrophages, Proprotein, Receptor, response, PC3 Prohormone, Laboratory Mouse, NEOPLASMS BENIGN, Neoplasia, RWDD52305http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023533dbgap_ncbi~0patentfamilies~0rfam~0merops~0complex-portal~0uniprot~0wormbaseparasite~0embl-covid19~0reactome~0emdb~0wgs_masters~0ebiweb_resources~0opentargets_genetics~0biomodels_all~0ipd-mhc~0ebiweb_teams~0taxonomy~0genome_assembly~0sc-experiments~0ebiweb_people~0enzymeportal_enzymes~0ipd-nhkir~0cellosaurus~0pdbe~0chebi~0patentproteins~0interpro7~0uniref~0chembl~0pdbekb~0gpcrdb~0hgnc~0sc-genes~0intact~0rhea~0ebiweb_training~0alphafold~0imgt-hla~0patentnucleotides~0ensemblroot~0eva_studies~0non-coding~0europepmc~0pubmed~1identifiers_registry~0pdbechem~0hpa-covid19~0eva-variants-covid19~0biosamples~0gwas_catalog~0biotools~0tls_masters~0mesh~0coding~0sra~0opentargets~0efo~0embl-pathogen~0project~0pride~1human_diseases~0geo_datasets~0embl~0treefam~0uniparc~0ols~0dgva~0intenz~0go~0tsa_masters~0biosamples-covid19~0ebiweb_corporate~0omim~0lrg~0earlycause-molecular-sequences~0ipd-kir~0empiar~0rnacentral~0orcid_data_claims~0gpmdb~2lineage-covid19~0metagenomics~0pfam~0pride archive~1varsite~00Resource Reanalysis0.00.00.0070943861813695250.01.0falseMolecular consequences of proprotein convertase 1/3 inhibition in macrophages for application to cancer immunotherapy: a proteomic studyData from ProteomeXchange, PXD ID: PXD001984. File: KO_LPS1.mzml. Published as part of Mol Cell Proteomics. 2015 Sep 1 . From the Abstract: {{i}} ... Here, we investigated the intracellular impact of the down-regulation of the proprotein convertase 1/3 in NR8383 macrophages. A complete proteomic study of secretomes and intracellular proteins was undertaken and revealed that inhibition of proprotein convertase 1/3 orient macrophages toward an M1 activated phenotype ... {{/i}}2015-09-11GPM3231002353326330543PXD001984PXD001984