Re: Antiangiogenic activity of prostate-specific antigen.

Although prostate-specific antigen (PSA) has been shown by Fortier et al. (1) to inhibit endothelial cell proliferation, migration, and invasion as well as metastatic spread, the value of these findings has to be questioned. This skepticism is due to the fact that, in all the experiments carried out, very high concentrations of PSA—equivalent to many thousands of ng/mL—were used. These high concentrations are very uncommon in humans, since the vast majority of men with prostate cancer have PSA levels well below 1000 ng/mL (2–4). More importantly, patients will experience symptomatic metastatic disease at PSA levels that are a fraction of those used in the experiments carried out by the authors (5–7). Hence, it is difficult to state whether, in the vast majority of patients with prostate cancer, PSA has any antiangiogenic or antimetastatic properties. It would have been far more informative if the authors had used concentrations of PSA that more closely reflect the levels detected in patients with prostate cancer. Without this information, it is too speculative to consider that elevations of PSA may be a defense against cancer progression and that the administration of PSA may be a rational therapeutic approach in the treatment of prostate cancer.