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).