title: Syndecan-1 regulates the biological activities of interleukin-34.
abstract: IL-34 is a challenging cytokine sharing functional similarities with M-CSF through M-CSFR activation. It also plays a singular role that has recently been explained in the brain, through a binding to the receptor protein tyrosine phosphatase RPTPβ/ζ. The aim of this paper was to look for alternative binding of IL-34 on other cell types. Myeloid cells (HL-60, U-937, THP-1) were used as cells intrinsically expressing M-CSFR, and M-CSFR was expressed in TF-1 and HEK293 cells. IL-34 binding was studied by Scatchard and binding inhibition assays, using 125I-radiolabelled cytokines, and surface plasmon resonance. M-CSFR activation was analysed by Western blot after glycosaminoglycans abrasion, syndecan-1 overexpression or repression and addition of a blocking anti-syndecan antibody. M-CSF and IL-34 induced different patterns of M-CSFR phosphorylations, suggesting the existence of alternative binding for IL-34. Binding experiments and chondroitinase treatment confirmed low affinity binding to chondroitin sulphate chains on cells lacking both M-CSFR and RPTPβ/ζ. Amongst the proteoglycans with chondroitin sulphate chains, syndecan-1 was able to modulate the IL-34-induced M-CSFR signalling pathways. Interestingly, IL-34 induced the migration of syndecan-1 expressing cells. Indeed, IL-34 significantly increased the migration of THP-1 and M2a macrophages that was inhibited by addition of a blocking anti-syndecan-1 antibody. This paper provides evidence of alternative binding of IL-34 to chondroitin sulphates and syndecan-1 at the cell surface that modulates M-CSFR activation. In addition, IL-34-induced myeloid cell migration is a syndecan-1 dependent mechanism.
authors: INSERM, UMR 957, Equipe Ligue 2012, Nantes F-44035, France; Université de Nantes, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, France.
authors: Aude I
authors: AI
authors: Segaliny
authors: INSERM, UMR 957, Equipe Ligue 2012, Nantes F-44035, France; Université de Nantes, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, France; Centre hospitalier universitaire de Nantes, France.
authors: Regis
authors: R
authors: Brion
authors: INSERM, U892, CNRS, U6299, Centre de Recherche en Cancérologie Nantes-Angers, équipe Cytokines et Récepteurs en Immuno-Hémato-Cancérologie, Université de Nantes, France.
authors: Erwan
authors: E
authors: Mortier
authors: INSERM, U892, CNRS, U6299, Centre de Recherche en Cancérologie Nantes-Angers, équipe Cytokines et Récepteurs en Immuno-Hémato-Cancérologie, Université de Nantes, France.
authors: Mike
authors: M
authors: Maillasson
authors: INSERM, U892, CNRS, U6299, Centre de Recherche en Cancérologie Nantes-Angers, équipe Recherche en Oncologie Nucléaire, Université de Nantes, Nantes, France.
authors: Michel
authors: M
authors: Cherel
authors: INSERM, U892, CNRS, U6299, Centre de Recherche en Cancérologie Nantes-Angers, équipe Cytokines et Récepteurs en Immuno-Hémato-Cancérologie, Université de Nantes, France.
authors: Yannick
authors: Y
authors: Jacques
authors: INSERM, UMR 957, Equipe Ligue 2012, Nantes F-44035, France; Université de Nantes, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, France; Centre hospitalier universitaire de Nantes, France.
authors: Benoît
authors: B
authors: Le Goff
authors: INSERM, UMR 957, Equipe Ligue 2012, Nantes F-44035, France; Université de Nantes, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, France; Centre hospitalier universitaire de Nantes, France. Electronic address: dominique.heymann@univ-nantes.fr.
authors: Dominique
authors: D
authors: Heymann
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008954:Models, Biological; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D053668:Syndecan-1 / Q000378:metabolism*
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D034741:RNA, Small Interfering; D053668:Syndecan-1; D016173:Macrophage Colony-Stimulating Factor; D002809:Chondroitin Sulfates; D016186:Receptor, Macrophage Colony-Stimulating Factor; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: Co-receptor chondroitin sulphate; Cytokine bioavailability; Interleukin-34; M-CSFR; M2a macrophage; Syndecan-1