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Prostate-specific antigen activates single-chain urokinase-type plasminogen activator
International Journal of Cancer
|December 11, 1995
Summary
Prostate-specific antigen (PSA) activates urokinase-type plasminogen activator (uPA), a key factor in prostate cancer spread. This discovery suggests PSA initiates the cascade driving tumor invasion and metastasis.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Prostate-specific antigen (PSA) is a tumor marker for prostate cancer.
- Prostate cancer cells over-express urokinase-type plasminogen activator (uPA), crucial for tumor invasion and metastasis.
Purpose of the Study:
- To investigate the interaction between PSA and single-chain uPA (scuPA).
- To determine if PSA can activate scuPA and influence prostate cancer progression.
Main Methods:
- Incubation of scuPA with PSA.
- Measurement of active uPA using a synthetic substrate (S-2444).
- SDS-PAGE and amino-acid-sequence analysis to identify cleavage sites.
Main Results:
- PSA dose- and time-dependently activated scuPA.
- PSA cleaved scuPA at Lys158-Ile159, generating active 2-chain uPA.
- PSA did not alter the activity of the 2-chain uPA form.
Conclusions:
- PSA acts as an initiator of prostate cancer invasion and metastasis by activating uPA.
- This finding provides new insights into the molecular mechanisms of prostate cancer progression.