A ligand-free, soluble urokinase receptor is present in the ascitic fluid from patients with ovarian cancer.

Abstract

We have identified a soluble form of the human urokinase plasminogen activator (uPA) receptor (uPAR) in the ascitic fluids from patients with ovarian cancer. After purification of uPAR from the ascitic fluids by ligand-affinity chromatography (prouPA Sepharose), the uPAR was initially identified by crosslinking to a radiolabeled amino-terminal fragment of human uPA. The uPAR purified from the ascitic fluid has no bound ligand (uPA), as similar amounts can be purified by ligand-affinity chromatography as by immuno-affinity chromatography. uPAR from ascitic fluids partitions in the water phase after a temperature-dependent phase separation of a detergent extract. It therefore lacks at least the lipid moiety of the glycophospholipid anchor present in cellular-bound uPARs. It is highly glycosylated and the deglycosylated form has the same electrophoretic mobility as previously characterized cellular uPAR from other sources. The immunoreactivity of the purified uPAR from the ascitic fluid is indistinguishable from that of characterized uPAR, demonstrated by Western blotting with three different anti-uPAR monoclonal antibodies. The uPAR was found in 11 of 11 ascitic fluids from patients with ovarian cancer and in elevated amounts in the plasma from 2 of 3 patients. The concentration of soluble uPAR in the ascitic fluid was estimated to range between 1 and 10 ng/ml. Human soluble uPAR, derived from the tumor cells, was also found in the ascitic fluid and serum from nude mice xenografted intraperitoneally with three different human ovarian carcinomas. (J. Clin. Invest. 1993.92:2160-2167.) Key words: ovarian cancer. urokinase plasminogen activator receptor * ascitic fluid * plasma.soluble receptor

Urokinase-type Plasminogen Activator Receptor (CD87) Is a Ligand for Integrins and Mediates Cell-Cell Interaction

“…Soluble uPAR is present in ascites of ovarian cancer patients (55). Soluble uPAR levels in plasma increase in patients with rheumatoid arthritis (56), ovarian cancer (57), and leukemia (58).…”

Ascites induces modulation of α6β1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma

“…In ovarian cancer, a strong correlation has been reported between urokinase plasminogen activator (uPA) antigen levels and poor prognosis (Konecny et al, 2001) and uPA is localised in primary and metastatic ovarian cancer specimens, as well as in the conditioned medium of many (but not all) ovarian cancer cell lines (Ahmed et al, 2002b). In addition, ovarian cancer patient's tumour fluid expresses a higher concentration of cell-free urokinase plasminogen activator receptor (uPAR) (Pedersen et al, 1993) and high levels of cell-associated uPA correlate with advance stage disease (Tecimer et al, 2000).…”

Soluble Urokinase-type Plasminogen Activator Receptor Inhibits Cancer Cell Growth and Invasion by Direct Urokinase-independent Effects on Cell Signaling

“…In humans, SuPAR is normally found in the plasma; however, the level of SuPAR may be dramatically increased in patients with various forms of malignancy, including ovarian cancer, non-small cell lung cancer, leukemia, colon cancer, and breast cancer (35)(36)(37)(38)(39)(40)(41)(42)(43). These studies provide compelling evidence that soluble uPAR is present in the microenvironment of malignant cells.…”