PLoS ONE (Jan 2012)

Effect of lumican on the migration of human mesenchymal stem cells and endothelial progenitor cells: involvement of matrix metalloproteinase-14.

  • Mariusz Malinowski,
  • Katarzyna Pietraszek,
  • Corinne Perreau,
  • Mateusz Boguslawski,
  • Véronique Decot,
  • Jean-François Stoltz,
  • Laurent Vallar,
  • Jolanta Niewiarowska,
  • Czeslaw Cierniewski,
  • François-Xavier Maquart,
  • Yanusz Wegrowski,
  • Stéphane Brézillon

DOI
https://doi.org/10.1371/journal.pone.0050709
Journal volume & issue
Vol. 7, no. 12
p. e50709

Abstract

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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).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.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.