title: Lumican inhibits angiogenesis by interfering with α2β1 receptor activity and downregulating MMP-14 expression.
abstract: BACKGROUND
  Previous studies showed that lumican, a small leucine-rich proteoglycan that binds to α2 integrin I domain, is an efficient inhibitor of cell adhesion and migration. In this report, we tested its effect on angiogenesis in vitro and in vivo.
  
  
  METHODS
  Effect of lumican on angiogenesis was evaluated by in vitro capillary tube formation test performed between Fibrin II Gels or in Matrigel™ and in vivo by Matrigel(™) plug assay in BALB/c mice. Changes in matrix metalloproteinases expression caused by lumican were analyzed in endothelial cells by real-time PCR, Western immunoblotting and gelatin zymography.
  
  
  RESULTS
  In unchallenged endothelial cells, Matrigel™ induced robust capillary morphogenesis. In contrast, tube formation was dramatically reduced by lumican, and by siRNA to β1 integrin subunit mRNA but not by control siRNA. Similarly, lumican effectively inhibited neovascularization in vivo in assays using Matrigel™ plugs formed in BALB/c mice. Interestingly, lumican significantly reduced expression of matrix metalloproteinases, particularly MMP-14 that is known to activate other MMPs in close vicinity of endothelial cell membranes.
  
  
  CONCLUSIONS
  Our results provide strong evidence that lumican affects angiogenesis both by interfering with α2β1 receptor activity and downregulating proteolytic activity associated with surface membranes of endothelial cells.
authors.affiliation: Department of Molecular and Medical Biophysics, Medical University of Lodz, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Niewiarowska
authors.forename: Stéphane
authors.initials: S
authors.lastname: Brézillon
authors.forename: Izabela
authors.initials: I
authors.lastname: Sacewicz-Hofman
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Bednarek
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Maquart
authors.forename: Mariusz
authors.initials: M
authors.lastname: Malinowski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wiktorska
authors.forename: Yanusz
authors.initials: Y
authors.lastname: Wegrowski
authors.forename: Czeslaw S
authors.initials: CS
authors.lastname: Cierniewski
mesh_terms: D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics; D007632:Keratan Sulfate / Q000494:pharmacology*; D000071234:Lumican; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D038982:Integrin alpha2beta1; D019012:Integrin beta1; C000604307:Lum protein, mouse; D000071234:Lumican; D061965:Matrix Metalloproteinase Inhibitors; C507096:Mmp14 protein, mouse; D034741:RNA, Small Interfering; D007632:Keratan Sulfate; D053511:Matrix Metalloproteinase 14