Soluble receptor for urokinase plasminogen activator in both full-length and a cleaved form is present in high concentration in cystic fluid from ovarian cancer

Abstract

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, approximately 10-fold higher than the concentration in ascitic fluid and approximately 100-fold higher than that in blood. Also, the concentration in malignant cysts was approximately 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.