Prostate-Specific Antigen is Angiogenesis/Tumorigenic or Anti-angiogenic/Anti-metastatic?
Anti-angiogenic properties of prostate‐specific antigen
The prostate produces high levels of prostate‐specific antigen (PSA, also known as kallikrein‐related peptidase 3, KLK3), which is a potential target for tumor imaging and treatment. Although serum PSA levels are elevated in prostate cancer, PSA expression is lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors. PSA has been shown to inhibit angiogenesis both in in vitro and in vivo models.
In this review we focus on our recent studies concerning the mechanism of the antiangiogenic function of PSA. We have recently shown that the antiangiogenic activity of PSA is related to its enzymatic activity. Inactive PSA isoforms do not have antiangiogenic activity as studied by a human umblical vein endothelial cell (HUVEC) tube formation model. Furthermore, inhibition of PSA, either by a monoclonal antibody or small molecule inhibitors abolishes the effect of PSA, while a peptide that stimulates the activity of PSA enhaces the antiangiogenic effect. We have analyzed changes in gene expression associated with the PSAinduced reduction of tube formation in the HUVEC model. Several small changes were observed and they were found to be opposite to those associated with tube formation.
Taken together, these studies suggest that PSA exerts antiantiogenic activity related to its enzymatic activity. Thus it might be associated with the slow growth of prostate cancer.
Anti-metastatic role of the prostate-specific antigen
Prostate-specific antigen stimulation enhance its anti-angiogenic activity
Interestingly, I was talking to someone whose PSA was rising and he was not worried about it. His reasoning was that PSA rises to prevent cancer from spreading. So when he tried various things to combat his prostate cancer, if he saw an immediate rise in PSA, he thought it could actually be a good thing.
Interesting research, I didn't realize PSA could have an antiangiogenic effect. I had seen it previously postulated that it may promote metastasis due to its proteolytic activity, but it was just theory. Of course, it doesn't seem to be protective enough to prevent growth or metastasis as the higher the PSA, the greater the chance of metastasis and the worse the situation. The exception is rare cases in which prostate cancer has regressed to be very stem-cell-like and produces little to no PSA. When therapy is effective for prostate cancer, PSA will often increase and then decrease, this is due to the release of PSA from dying prostate cells and the phenomenon is commonly seen in radiation and chemo for prostate cancer, however, a sustained rise in PSA is invariably associated with disease progression.