Prostate‐specific antigen activates single‐chain urokinase‐type plasminogen activator

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Abstract
Prostate-specific antigen (PSA) increases in the plasma of patients with prostate cancer, and has therefore been used as a reliable tumor marker. It has been demonstrated that prostate cancer cells over-express urokinase-type plasminogen activator (uPA), which plays an important role in tumor invasion and metastasis. We found that PSA converts the single-chain pro-form of urokinase-type plasminogen activator (scuPA) to an active 2–chain form. The active 2–chain uPA generated from scuPA by PSA was measured by hydrolyzation of S-2444, a synthetic substrate for uPA. PSA activated scuPA time- and dose-dependently. SDS-PAGE analysis revealed that, after incubation with PSA, the intensity of the 55–kDa band of scuPA decreased concomitantly with increases in the intensity of the 2 bands at 33 kDa and 22 kDa. Amino-acid-sequence analysis indicated that PSA cleaved Lys158-Ile159, which corresponds with the site cleaved by plasmin. PSA did not enhance or impair the activity of the 2–chain form of uPA. These findings imply that PSA could be an initiator of the protease cascade involved in prostate-cancer invasion and metastasis. © 1995 Wiley-Liss, Inc.