IN-VIVO AND IN-VITRO COMPLEX-FORMATION OF PROSTATE-SPECIFIC ANTIGEN WITH ALPHA(1)-ANTI-CHYMOTRYPSIN

Complex formation of prostate specific antigen (PSA) with its inhibito r alpha(1)-anti-chymotrypsin (ACT) in vivo and in vitro was studied. P atients with benign prostatic hyperplasia (BPH) were treated with the computer assisted device ''Prostatron(R).'' This instrument acts by me ans of thermal destruction of prostatic tissue. The effect of the trea tment was followed by measurement of serum PSA concentrations using co mmercially available immunoassays from Roche (Cobas(R) Core), Wallac ( Delfia(R)) and Abbot (IMx(R)) and Hybritech Tandem(R). Serum samples w ere further analyzed by molecular sieving on S.300 (Pharmacia) and ana lyzed for PSA by immune assay. The complex formation of PSA with ACT i n serum was studied, demonstrating this process to be influenced by ex ternal stimulus. Patient sera revealing initially normal PSA levels (3 to 5 ng/ml) were stimulated to very high levels of PSA (greater than or equal to 140 ng/ml) by Prostatron(R) treatment. The absolute PSA le vel depends on the assay system and not only on the staging of the pro state tumor. In addition, complex formation was studied in athymic nud e mice and in vitro revealing the possible pathways of PSA release. PS A from LNCAP cells kept in vitro show predominantly uncomplexed (free) PSA, whereas PSA from LNCAP cells injected into nude mice appears in the serum of the animals in complexed form. This demonstrates how in t he immunization process free and complexed PSA serve as antigens in th e standard procedure for the production of antisera for PSA. This mode l system also can be used for studies of the release mechanism of PSA into blood circulation. (C) 1995 Wiley-Liss, Inc.