Blockage of urokinase receptor reduces in vitro the motility and the deformability of endothelial cells.
The binding of urokinase (u-PA) to its cell surface receptor (u-PAR) is critical for tumor cell invasion. Here, we report that the distribution of this binding by a u-PAR antagonist ATF-HSA inhibits in vitro the motility of endothelial cells in a dose-dependent manner. This inhibition was also observed when the cells were first stimulated with potent angiogenic factors, including bFGF or VEGF. [3H]thymidine incorporation assay demonstrated that ATF-HSA did not affect the cell proliferation. ATF-HSA was more potent than plasmin inhibitors, suggesting that it exerts its effects not solely by inhibiting the remodeling of the extracellular matrix. In fact, analysis of the cell shape change during migration revealed for the first time that its effect is related to a decrease in cell deformability. These results suggest that u-PAR antagonist may be a new approach to control angiogenesis.
Lu
H
H
INSERM U353, Hôpital St. Louis, Paris, France.
Mabilat
C
C
Yeh
P
P
Guitton
J D
JD
Li
H
H
Pouchelet
M
M
Shoevaert
D
D
Legrand
Y
Y
Soria
J
J
Soria
C
C
D007611:Aprotinin / Q000494:pharmacology; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology; D010446:Peptide Fragments; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D014471:Umbilical Veins; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D007611:Aprotinin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator