Blockage of urokinase receptor reduces in vitro the motility and the deformability of endothelial cells

H Lu; C Mabilat; P Yeh; J D Guitton; H Li; M Pouchelet; D Shoevaert; Y Legrand; J Soria; C Soria

doi:10.1016/0014-5793(95)01540-x

Blockage of urokinase receptor reduces in vitro the motility and the deformability of endothelial cells

FEBS Lett. 1996 Feb 12;380(1-2):21-4. doi: 10.1016/0014-5793(95)01540-x.

Authors

H Lu¹, C Mabilat, P Yeh, J D Guitton, H Li, M Pouchelet, D Shoevaert, Y Legrand, J Soria, C Soria

Affiliation

¹ INSERM U353, Hôpital St. Louis, Paris, France.

PMID: 8603739
DOI: 10.1016/0014-5793(95)01540-x

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aprotinin / pharmacology
Cell Division
Cell Movement / drug effects
Cell Movement / physiology*
Cell Size
Endothelial Growth Factors / pharmacology
Endothelium, Vascular / cytology*
Enzyme Inhibitors / pharmacology
Fibrinolysin / antagonists & inhibitors
Fibroblast Growth Factor 2 / pharmacology
Humans
Lymphokines / pharmacology
Peptide Fragments
Receptors, Cell Surface / antagonists & inhibitors
Receptors, Cell Surface / physiology*
Receptors, Urokinase Plasminogen Activator
Recombinant Fusion Proteins
Serum Albumin
Umbilical Veins
Urokinase-Type Plasminogen Activator / physiology*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Substances

Endothelial Growth Factors
Enzyme Inhibitors
Lymphokines
PLAUR protein, human
Peptide Fragments
Receptors, Cell Surface
Receptors, Urokinase Plasminogen Activator
Recombinant Fusion Proteins
Serum Albumin
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Fibroblast Growth Factor 2
Aprotinin
Fibrinolysin
Urokinase-Type Plasminogen Activator