High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian cancer cells reduces intraperitoneal tumor growth and spread in nudemice

Focussing of the serine protease urokinase (uPA) to the tumor cell surface via interaction with its receptor (uPAR) is an important step in tumor inva sion and metastasis. The human ovarian cancer cell line OV-MZ-6#8 was stabl y transfected with expression plasmids either encoding cell-associated uPAR (GPI-uPAR) or a soluble form of uPAR (suPAR) lacking its glycan lipid anch or. In vitro, high level synthesis of functionally active recombinant suPAR inhibited cell proliferation and led to reduced cell-associated fibrin mat rix degradation, whereas fibrinolytic activity was increased in OV-MZ-6#8 c ells overexpressing GPI-uPAR. Both OV-MZ-6#8-derived clones were inoculated into the peritoneum of nude mice and tested for tumor growth and spread, H igh level synthesis of recombinant suPAR (without altering the physiologica l expression levels of GPI-uPAR and uPA in these cells) resulted in a signi ficant reduction of tumor burden (up to 86%) in the xenogeneic mouse model. In contrast, overexpression of GPI-uPAR in tumor cells did not affect tumo r growth. Our results demonstrate that high levels of suPAR in the ovarian cancer cell vicinity can act as a potent scavenger for uPA, thereby signifi cantly reducing tumor cell growth and cancer progression in vivo.