Detection of soluble urokinase receptor by immunoradiometric assay and its application in tumor patients

It has recently been found that tumor cells express large amounts of urokinase receptor (uPAR) on their surface and that the blood soluble uPAR (suPAR) level in cancer patients is increased. However, the significance of suPAR in tumor progression is still unclear. To investigate the significance of suPAR in evaluating clinical status of solid tumor patients, an immunoradiometric assay (IRMA) based on using two monoclonal antibodies (McAbs) to different epitopes of uPAR was established to determine the serum levels of suPAR in normal individuals and solid tumor patients. The detectable range of this suPAR IRMA was 1.95-500 mug/l. The affinity constant was 4.75 x 10(9) l/mol. The mean rate of recovery was 101.3%, and the mean coefficients of variation for intra- and interassay were 6.40 +/-2.57% (mean +/-S.D, n=11) and 10.48 +/-2.65% (n=5), respectively. The serum suPAR levels were 2.71 +/-1.12 mug/l in 62 normal individuals, 3.71 +/-1.69 mug/l in 30 patients with benign tumors, and 5.82 +/-2.27 mug/l in 124 patients with malignant tumors. The serum suPAR levels of these two types of tumor patients were increased in comparison with that of normal individuals (P values less than .01 and .001). The extent of their increase in malignant tumors was much greater than in benign tumors (P<.001). The serum suPAR levels of patients with malignant tumors were correlated with tumor invasion, metastasis, and surgical intervention. Our data suggest that IRMA for suPAR could be a sensitive and specific assay and that the serum suPAR level would be a valuable index for evaluating the condition and prognosis of tumor patients in clinic. <(c)> 2001 Elsevier Science Ltd. All rights reserved.