TY - JOUR
T1 - Effect of Lumican on the Migration of Human Mesenchymal Stem Cells and Endothelial Progenitor Cells
T2 - Involvement of Matrix Metalloproteinase-14
AU - Malinowski, Mariusz
AU - Pietraszek, Katarzyna
AU - Perreau, Corinne
AU - Boguslawski, Mateusz
AU - Decot, Véronique
AU - Stoltz, Jean François
AU - Vallar, Laurent
AU - Niewiarowska, Jolanta
AU - Cierniewski, Czeslaw
AU - Maquart, François Xavier
AU - Wegrowski, Yanusz
AU - Brézillon, Stéphane
AU - Karamanos, Nikos K.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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). Methodology/Principal Findings: 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. Conclusion/Significance: 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.
AB - 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). Methodology/Principal Findings: 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. Conclusion/Significance: 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.
UR - http://www.scopus.com/inward/record.url?scp=84870858903&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0050709
DO - 10.1371/journal.pone.0050709
M3 - Article
C2 - 23236386
AN - SCOPUS:84870858903
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e50709
ER -