Document Detail


Inhibition of endothelial cell movement and tubulogenesis by human recombinant soluble melanotransferrin: involvement of the u-PAR/LRP plasminolytic system.
MedLine Citation:
PMID:  15843038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously demonstrated that human recombinant soluble melanotransferrin (hr-sMTf) interacts with the single-chain zymogen pro urokinase-type plasminogen activator (scu-PA) and plasminogen. In the present work, the impact of exogenous hr-sMTf on endothelial cells (EC) migration and morphogenic differentiation into capillary-like structures (tubulogenesis) was assessed. hr-sMTF at 10 nM inhibited by 50% the migration and tubulogenesis of human microvessel EC (HMEC-1). In addition, in hr-sMTf-treated HMEC-1, the expression of both urokinase-type plasminogen activator receptor (u-PAR) and low-density lipoprotein receptor-related protein (LRP) are down-regulated. However, fluorescence-activated cell sorting analysis revealed a 25% increase in cell surface u-PAR in hr-sMTf-treated HMEC-1, whereas the binding of the urokinase-type plasminogen activator (u-PA)*plasminogen activator inhibitor-1 (PAI-1) complex is decreased. This reduced u-PA-PAI-1 binding is correlated with a strong inhibition of the HMEC-1 plasminolytic activity, indicating that exogenous hr-sMTf treatment alters the internalization and recycling processes of free and active u-PAR at the cellular surface. Overall, these results demonstrate that exogenous hr-sMTf affects plasminogen activation at the cell surface, thus leading to the inhibition of EC movement and tubulogenesis. These results are the first to consider the potential use of hr-sMTf as a possible therapeutic agent in angiogenesis-related pathologies.
Authors:
Jonathan Michaud-Levesque; Yannève Rolland; Michel Demeule; Yanick Bertrand; Richard Béliveau
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-11-11
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1743     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-21     Completed Date:  2005-06-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  243-53     Citation Subset:  IM    
Affiliation:
Laboratoire de Médecine Moléculaire, Service d'Hémato-Oncologie, Hôpital Ste-Justine-UQAM, C.P. 8888, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Neoplasm
Cell Membrane / drug effects,  metabolism
Cell Movement / drug effects
Cells, Cultured
Down-Regulation
Endothelial Cells / drug effects*,  physiology
Humans
LDL-Receptor Related Proteins / metabolism*
Microtubules / physiology
Neoplasm Proteins / pharmacology*
Plasminogen Activator Inhibitor 1 / metabolism
Receptors, Cell Surface / metabolism*
Receptors, Urokinase Plasminogen Activator
Recombinant Proteins / pharmacology
Urokinase-Type Plasminogen Activator / metabolism
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/LDL-Receptor Related Proteins; 0/Neoplasm Proteins; 0/PLAUR protein, human; 0/Plasminogen Activator Inhibitor 1; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; 0/Recombinant Proteins; 0/melanoma-specific antigens; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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