RECOMBINANT SOLUBLE UROKINASE RECEPTOR AS A SCAVENGER FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (UPA) - INHIBITION OF PROLIFERATION AND INVASION OF HUMAN OVARIAN-CANCER CELLS

A recombinant soluble human urokinase receptor comprising amino acids 1-277 was cloned and transfected into CHO cells. The mutant protein (r ec-uPAR(277)), purified from the CHO cell supernatant by affinity chro matography on immobilized urokinase (uPA), in a four-fold excess, comp letely abolished the binding of FITC-labeled pro-uPA to the human ovar ian cancer cell line, OV-MZ-6. This invasive and tumorigenic cancer ce ll line expresses uPA, its inhibitor PAI-1, and the high-affinity rece ptor for uPA, uPAR. Rec-uPAR(277) significantly reduced the proliferat ion of OV-MZ-6 cells in a concentration-dependent manner without alter ing the viability of the cells. Invasion of OV-MZ-6 cells tested in an in vitro Matrigel invasion assay was inhibited by rec-uPAR(277) up to 75%. In conclusion, these results demonstrate that rec-uPAR(277) can function as a scavenger for uPA in vitro by inhibiting proliferation a nd invasion of human cancer cells.