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

被引:110
作者
WILHELM, O [1 ]
WEIDLE, U [1 ]
HOHL, S [1 ]
RETTENBERGER, P [1 ]
SCHMITT, M [1 ]
GRAEFF, H [1 ]
机构
[1] BOEHRINGER MANNHEIM GMBH,D-82377 PENZBERG,GERMANY
关键词
UROKINASE RECEPTOR; INVASION; PROLIFERATION; OVARIAN CANCER;
D O I
10.1016/0014-5793(94)80259-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A recombinant soluble human urokinase receptor comprising amino acids 1-277 was cloned and transfected into CHO cells. The mutant protein (rec-uPAR(277)), 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-uPAR(277) 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-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 and invasion of human cancer cells.
引用
收藏
页码:131 / 134
页数:4
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