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

FEBS Lett. 1994 Dec 12;356(1):56-9. doi: 10.1016/0014-5793(94)01237-7.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cloning, Molecular
  • Humans
  • Kluyveromyces / genetics
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Plasminogen / antagonists & inhibitors*
  • 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
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / pharmacology*

Substances

  • PLAUR protein, human
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Recombinant Fusion Proteins
  • Serum Albumin
  • Plasminogen
  • Urokinase-Type Plasminogen Activator