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Soluble Receptor for Urokinase Plasminogen Activator in Both Full-Length and a Cleaved Form Is Present in High Concentration in Cystic Fluid from Ovarian Cancer¹

Department of Obstetrics and Gynecology, University Hospital, S-221 85 Lund, Sweden [K. W., B. C.]; and Finsen Laboratory, Rigshospitalet, DK-2100, Copenhagen, Denmark [G. H-H.]

We assayed the levels of soluble urokinase plasminogen activator receptor (su-PAR) with an ELISA in various body fluids from 77 patients with benign or malignant ovarian tumors, histologically classified as follows: benign; possibly malignant (borderline); and well, intermediately, and poorly differentiated malignant. The concentration of su-PAR in fluid from malignant cysts was extremely high, 10-fold higher than the concentration in ascitic fluid and 100-fold higher than that in blood. Also, the concentration in malignant cysts was 10-fold higher than the concentration in benign cysts. Such high concentrations of su-PAR were found not only in truly malignant but also in possibly malignant cysts. Thus, we suggest that the concentration of su-PAR in cystic fluid can serve as a marker, allowing early diagnosis of malignant ovarian cysts. The concentration of su-PAR in fluid aspirated transvaginally with ultrasonographic guidance can be used to discriminate possibly and truly malignant cysts from benign cysts without surgery.

The high concentrations of su-PAR in ovarian cystic fluids allowed us to characterize the molecular forms. Cross-linking of a radiolabeled ligand to the receptor demonstrated that at least a fraction of su-PAR was able to bind the ligand. A cleaved form of the receptor constituting domains 2 and 3 was detected with Western blotting. The cleaved receptor, which is devoid of the ligand-binding domain 1, has not previously been demonstrated in body fluids; it has only been demonstrated on cell surfaces. su-PAR domains 2 and 3 were found in cystic fluids from both malignant and benign ovarian tumors.

¹ This work was supported by the Swedish Cancer Fund (Grant 2693-B96-07XBB); the Lund University Medical Faculty; the Lund University Hospital Fund for Cancer Research; and the Gunnar, Arvid, and Elisabeth Nilssons Fund for Cancer Research.

² To whom requests for reprints should be addressed.

Received 2/ 2/98. Accepted 6/ 2/98.

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