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

• Published in: FEBS letters 1994-12, Vol.356 (1), p.56-59
• Main Authors: Lu, He, Yeh, Patrice, Guitton, Jean-Dominique, Mabilat, Christelle, Desanlis, Francine, Maury, Isabelle, Legrand, Yves, Soria, Jeannette, Soria, Claudine
• Format: Article
• Language: English
• Subjects: Cell Line; Cloning, Molecular; Humans; Hybrid protein; Kluyveromyces - genetics; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Plasminogen - antagonists & inhibitors; Plasminogen activation; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Urokinase Plasminogen Activator; Recombinant Fusion Proteins - pharmacology; Saccharomyces cerevisiae - genetics; Serum Albumin - genetics; Serum Albumin - pharmacology; Tumor Cells, Cultured; Tumor metastasis; Urokinase receptor antagonist; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)01237-7

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).