Saturation of tumour cell surface receptors for urokinase-type plasminogen activator by amino-terminal fragment and subsequent effect on reconstituted basement membranes invasion

Abstract

Single-chain urokinase-type plasminogen activator (pro-uPA) is bound to a specific surface receptor on ovarian cancer HOC-I cells that is incompletely saturated. Saturation of uncovered receptors by uPA polypeptides with intact amino-terminal fragment (ATF) derived from pro-uPA by limited proteolysis (human leucocyte elastase [HLE] or V8 protease) has been studied. HOC-I cells preferentially invaded reconstituted basement membranes in a time- and plasminogen-dependent manner. This process was inhibitable by preincubation with uPA polypeptides in the medium at levels which suggested that complete saturation of cell surface uPA receptors occurred. This result indicates that occupation of uPA receptors by enzymatically inactive uPA fragments or prevention of rebinding of pro-uPA synthesised by tumour cells to the receptors specifically reduces the invasion of the tumour cells through basement membranes in vitro.