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 inhibitor alpha(1)-anti-chymotrypsin (ACT) in vivo and in vitro was studied. Patients with benign prostatic hyperplasia (BPH) were treated with the computer assisted device ''Prostatron(R).'' This instrument acts by means of thermal destruction of prostatic tissue. The effect of the treatment was followed by measurement of serum PSA concentrations using commercially available immunoassays from Roche (Cobas(R) Core), Wallac (Delfia(R)) and Abbot (IMx(R)) and Hybritech Tandem(R). Serum samples were further analyzed by molecular sieving on S.300 (Pharmacia) and analyzed for PSA by immune assay. The complex formation of PSA with ACT in serum was studied, demonstrating this process to be influenced by external 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 level depends on the assay system and not only on the staging of the prostate tumor. In addition, complex formation was studied in athymic nude mice and in vitro revealing the possible pathways of PSA release. PSA 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 the immunization process free and complexed PSA serve as antigens in the standard procedure for the production of antisera for PSA. This model system also can be used for studies of the release mechanism of PSA into blood circulation. (C) 1995 Wiley-Liss, Inc.