Patients with advanced
prostate cancer frequently have a poor prognosis as a result of
metastasis. The serum
prostate-specific antigen (PSA) test is widely used for the diagnosis of
prostate cancer. The enzymatic activity of PSA may be involved in the invasion of
prostate cancer. We set out to determine the prevalent form of PSA in human prostate
adenocarcinoma samples by ELISA and Western blot analysis and its enzymatic activity using a synthetic substrate
S-2586 and
fibronectin. Our results show that in serum from
prostate cancer patients and in tumour homogenates, the prevalent form was PSA bound to alpha1-antichymotrypsin. All homogenates showed enzymatic activity towards a synthetic PSA substrate, whereas only five samples showed activity at 28 kDa towards
fibronectin as determined by enzymography, which is most likely due to active PSA. Human
prostate cancer LNCaP cells produced largely inactive PSA. In comparison, 22Rv1 cells produced 29-fold less PSA, but with high specific activity. Similarly, our results from the human
prostate cancer tissue samples also show that free PSA appears to exist in diverse forms of very different specific activity. Since PSA, as a
serine protease, may be involved in the invasion of
prostate cancer, our results suggest that
prostate cancers have potentially diverse invasive capacity due to differences in specific enzymatic activity of PSA.