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 (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.
Wilhelm
O
O
Frauenklinik der TU München, Klinikum rechts der Isar, Germany.
Weidle
U
U
Höhl
S
S
Rettenberger
P
P
Schmitt
M
M
Graeff
H
H
D000818:Animals; D016466:CHO Cells; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D006224:Cricetinae; D003536:Cystadenocarcinoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator