Recombinant soluble urokinase receptor as a scavenger for urokinase‐type plasminogen activator (uPA)

Abstract

A recombinant soluble human urokinase receptor comprising amino acids 1–277 was cloned and transfected into CHO cells. The mutant protein (rec‐uPAR₂₇₇), purified from the CHO cell supernatant by affinity chromatography on immobilized urokinase (uPA), in a four‐fold excess, completely abolished the binding of FITC‐labeled pro‐uPA to the human ovarian cancer cell line, OV‐MZ‐6. This invasive and tumorigenic cancer cell line expresses uPA, its inhibitor PAI‐1, and the high‐affinity receptor for uPA, uPAR. Rec‐uPAR₂₇₇ significantly reduced the proliferation of OV‐MZ‐6 cells in a concentration‐dependent manner without altering the viability of the cells. Invasion of OV‐MZ‐6 cells tested in an in vitro Matrigel invasion assay was inhibited by rec‐uPAR₂₇₇ up to 75%. In conclusion, these results demonstrate that rec‐uPAR₂₇₇ can function as a scavenger for uPA in vitro by inhibiting proliferation and invasion of human cancer cells.