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

✍ Scribed by Etsuo Yoshida; Sayuri Ohmura; Masahiko Sugiki; Masugi Maruyama; Hisashi Mihara

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 497 KB
• Volume: 63
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910630618

✦ Synopsis

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 @PA), which plays an important role in tumor invasion and metastasis. We found that PSA converts the single-chain proform 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 L y ~' ~* -l l e ' * ~, 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.