| 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 |
Related Documents
:
|
9869168 - Evidence for the expression of urokinase-type plasminogen activator by human venous end... 3129438 - Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocali... 16272158 - Binding of pai-1 to endothelial cells stimulated by thymosin beta4 and modulation of th... 11157728 - Endothelial cells inhibit flow-induced smooth muscle cell migration: role of plasminoge... 18798868 - The ubiquitin c-terminal hydrolase uch-l1 regulates b-cell proliferation and integrin a... 1858848 - Clear zone in osteoclast function: role of podosomes in regulation of bone-resorbing ac... |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Proteolytic processing of TGFalpha redirects its mitogenic activity: the membrane-anchored form is a...
Next Document: The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway.