Blockage of the urokinase receptor on the cell surface: construction and characterization of a hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin.
Receptor-bound urokinase is likely to be a crucial determinant in both tumor invasion and angiogenesis. We report here that a yeast-derived genetic conjugate between human serum albumin and the 1-135 N-terminal residues of urokinase (u-PA) competitively inhibits the binding of exogenous and endogenous u-PA to its cell-anchored receptor (u-PAR). This hybrid molecule (ATF-HSA) also inhibits in vitro pro-urokinase-dependent plasminogen activation in the presence of u-PAR bearing cells. These effects are probably responsible for the observed in vitro inhibition of tumor cell invasion in a reconstituted basement membrane extract (Matrigel).
Lu
H
H
Unité INSERM 353, Hôpital St. Louis, Paris, France.
Yeh
P
P
Guitton
J D
JD
Mabilat
C
C
Desanlis
F
F
Maury
I
I
Legrand
Y
Y
Soria
J
J
Soria
C
C
D002460:Cell Line; D003001:Cloning, Molecular; D006801:Humans; D007716:Kluyveromyces / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D010958:Plasminogen / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012709:Serum Albumin / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000494:pharmacology*
C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator