Abstract

The plasminogen activators of surgically excised prostate cancers (43 specimens) and benign prostatic hyperplasias (33 specimens) were extracted with an acetate:arginine:detergent buffer, and the activities were quantitated with azocaseinolytic tests. Immunoinhibition with anti-urokinase antibody served to distinguish between activator types. The mean activator activities (total; urokinase type; and nonurokinase type) of the neoplastic group were about 2 times higher ( p < 0.05) than that of the benign prostatic hyperplasia tissues. Each group had more nonurokinase-type activator activity relative to urokinase type. Studies with autopsy tissues (13 specimens) revealed that different anatomical compartments of the prostate contain about the same mean activator activity, indicating that the site of origin of the disease did not influence the results. Immunoperoxidase staining for urokinase revealed its presence in the tumor cells and, to a lesser extent, in the epithelial elements of some benign ducts and glands but not in the connective tissue. The secretion and synthesis of activator activities were monitored in short-term ( 120 hr) organ cultures (serum-free media) of 21 neoplastic tissues. On the average, about 12 times more activity ( 80% as urokinase type) was recovered in the media and postculture tissue extracts than was present in preculture tissues. Similar results were observed with 10 benign prostatic hyperplasia specimens. Wide individual variations were present in both groups (1.5 to 322 times more activity than the initial values). Except for one case, urokinase-type activity was secreted continuously, while nonurokinase was secreted only initially in quantities similar to that present in preculture tissue extracts. After culture, tissue explants contained higher quantities of both activator activities than were present initially. Dexamethasone (10 or 100 µ M ) decreased secretion and/or synthesis of activators by about 70%. This human organ culture model appears to be a reproducible system for individual tissues and may prove to be a valuable tool for further studies. 1 Supported in part by Grant BC-235 from the American Cancer Society. 2 To whom requests for reprints should be addressed. 3 Eleanor Roosevelt Fellow of the International League against Cancer on leave from Miyazaki Medical College, Japan.