title: Effect of lumican on the migration of human mesenchymal stem cells and endothelial progenitor cells: involvement of matrix metalloproteinase-14.
abstract: BACKGROUND
  Increasing number of evidence shows that soluble factors and extracellular matrix (ECM) components provide an optimal microenvironment controlling human bone marrow mesenchymal stem cell (MSC) functions. Successful in vivo administration of stem cells lies in their ability to migrate through ECM barriers and to differentiate along tissue-specific lineages, including endothelium. Lumican, a protein of the small leucine-rich proteoglycan (SLRP) family, was shown to impede cell migration and angiogenesis. The aim of the present study was to analyze the role of lumican in the control of MSC migration and transition to functional endothelial progenitor cell (EPC).
  
  
  RESULTS
  Lumican inhibited tube-like structures formation on Matrigel® by MSC, but not EPC. Since matrix metalloproteinases (MMPs), in particular MMP-14, play an important role in remodelling of ECM and enhancing cell migration, their expression and activity were investigated in the cells grown on different ECM substrata. Lumican down-regulated the MMP-14 expression and activity in MSC, but not in EPC. Lumican inhibited MSC, but not EPC migration and invasion. The inhibition of MSC migration and invasion by lumican was reversed by MMP-14 overexpression.
  
  
  CONCLUSIONS
  Altogether, our results suggest that lumican inhibits MSC tube-like structure formation and migration via mechanisms that involve a decrease of MMP-14 expression and activity.
authors.affiliation: Laboratoire de Biochimie Médicale et de Biologie Moléculaire, CNRS FRE 3481, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Malinowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pietraszek
authors.forename: Corinne
authors.initials: C
authors.lastname: Perreau
authors.forename: Mateusz
authors.initials: M
authors.lastname: Boguslawski
authors.forename: Véronique
authors.initials: V
authors.lastname: Decot
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Stoltz
authors.forename: Laurent
authors.initials: L
authors.lastname: Vallar
authors.forename: Jolanta
authors.initials: J
authors.lastname: Niewiarowska
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Cierniewski
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Maquart
authors.forename: Yanusz
authors.initials: Y
authors.lastname: Wegrowski
authors.forename: Stéphane
authors.initials: S
authors.lastname: Brézillon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007632:Keratan Sulfate / Q000494:pharmacology*; D000071234:Lumican; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000494:pharmacology
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C000604306:LUM protein, human; D000071234:Lumican; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D007632:Keratan Sulfate; D053511:Matrix Metalloproteinase 14