title: Shed syndecan-2 inhibits angiogenesis.
abstract: Angiogenesis is essential for the development of a normal vasculature, tissue repair and reproduction, and also has roles in the progression of diseases such as cancer and rheumatoid arthritis. The heparan sulphate proteoglycan syndecan-2 is expressed on mesenchymal cells in the vasculature and, like the other members of its family, can be shed from the cell surface resulting in the release of its extracellular core protein. The purpose of this study was to establish whether shed syndecan-2 affects angiogenesis. We demonstrate that shed syndecan-2 regulates angiogenesis by inhibiting endothelial cell migration in human and rodent models and, as a result, reduces tumour growth. Furthermore, our findings show that these effects are mediated by the protein tyrosine phosphatase receptor CD148 (also known as PTPRJ) and this interaction corresponds with a decrease in active β1 integrin. Collectively, these data demonstrate an unexplored pathway for the regulation of new blood vessel formation and identify syndecan-2 as a therapeutic target in pathologies characterised by angiogenesis.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Rossi
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Alun R
authors.initials: AR
authors.lastname: Evans
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Kay
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Woodfin
authors.affiliation: Division of Biomedical Sciences, St. George's University of London, Cranmer Terrace, London SW17 0NE, UK.
authors.forename: Tristan R
authors.initials: TR
authors.lastname: McKay
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Sussan
authors.initials: S
authors.lastname: Nourshargh
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK j.whiteford@qmul.ac.uk.
authors.forename: James R
authors.initials: JR
authors.lastname: Whiteford
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D053669:Syndecan-2 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053669:Syndecan-2
keywords: Angiogenesis; Endothelial cell migration; Inflammation; Integrin; Syndecan