DETECTION AND CHARACTERIZATION OF THE PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PMSA) IN TISSUE-EXTRACTS AND BODY-FLUIDS

The prostate-specific membrane antigen (PSMA) glycoprotein is recogniz ed by the monoclonal antibody (MAb) 7E11-C5.3 as a predominant 100 kDa and minor 180 kDa component in LNCaP cell line extracts and its expre ssion has been shown by immunohistochemistry to be highly restricted t o prostate epithelium. The aim of the present study was to utilize Wes tern blot analysis to determine if PSMA could be detected in human tis sue extracts and body fluids and if so, which molecular forms were pre sent. PSMA was detected as 120 and 200 kDa bands in normal, benign and malignant prostate tissues and seminar plasma. Further analysis demon strated that the larger molecular form of PSMA may be a dimer of the l ower m.w. species. The PSMA glycoprotein was not detected in the major ity of nonprostate tissue extracts examined except for a low yet signi ficant amount in normal salivary gland, brain and small intestine, sug gesting that PSMA may not be as prostate-specific as originally though t. Since the prostate-specific antigen (PSA) has been shown to be maxi mally shed into the serum in high-grade and metastatic prostate carcin omas, it was surprising that PSMA could not be detected in serum by We stern blot analysis even in patients with actively progressive metasta tic disease. Second generation antibodies generated against different epitopes may be required to determine a PSMA is shed into serum. Our r esults support the hypothesis that PSMA is a novel prostate biomarker. (C) 1995 Wiley-Liss, Inc.