Urokinase type plasminogen activator receptor is involved in insulin-like growth factor-induced migration of rhabdomyosarcoma cells in vitro

2003 ◽  
Vol 197 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Marisa A. Gallicchio ◽  
Christoph Kaun ◽  
Johann Wojta ◽  
Bernd Binder ◽  
Leon A. Bach
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Insulin Like Growth Factor ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

scholarly journals Mannose 6-Phosphate/Insulin-like Growth Factor 2 Receptor Limits Cell Invasion by Controlling αVβ3 Integrin Expression and Proteolytic Processing of Urokinase-type Plasminogen Activator Receptor

2009 ◽  
Vol 20 (3) ◽  
pp. 745-756 ◽  
Author(s):  
Herbert B. Schiller ◽  
Andreas Szekeres ◽  
Bernd R. Binder ◽  
Hannes Stockinger ◽  
Vladimir Leksa
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Plasminogen Activator ◽  
Cell Invasion ◽  
Integrin Expression ◽  
Plasminogen Activation ◽  
Insulin Like Growth Factor ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Plasminogen Activator Receptor

The multifunctional mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is considered a tumor suppressor. We report here that RNA interference with M6P/IGF2R expression in urokinase-type plasminogen activator (uPA)/urokinase-type plasminogen activator receptor (uPAR) expressing human cancer and endothelial cells resulted in increased pericellular plasminogen activation, cell adhesion, and higher invasive potential through matrigel. M6P/IGF2R silencing led also to the cell surface accumulation of urokinase and plasminogen and enhanced expression of αV integrins. Genetic rescue experiments and inhibitor studies revealed that the enhanced plasminogen activation was due to a direct effect of M6P/IGF2R on uPAR, whereas increased cell adhesion to vitronectin was dependent on αV integrin expression and not uPAR. Increased cell invasion of M6P/IGF2R knockdown cells was rescued by cosilencing both uPAR and αV integrin. Furthermore, we found that M6P/IGF2R expression accelerates the cleavage of uPAR. M6P/IGF2R silencing resulted in an increased ratio of full-length uPAR to the truncated D2D3 fragment, incapable of binding most uPAR ligands. We conclude that M6P/IGF2R controls cell invasion by regulating αV integrin expression and by accelerating uPAR cleavage, leading to the loss of the urokinase/vitronectin/integrin-binding site on uPAR.

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