Finally! Why PSA levels reflect prostate cancer progression
Posted Jan 14 2011 12:00am
Although we have been using PSA to monitor the progression of prostate cancer and to test for risk of prostate cancer since the 1980s, we have never known exactly how PSA levels are associated with the increased growth of prostate cancer cells in the body.
Using human prostate cancer cells in a laboratory culture, Misra and his colleagues have been able to show that an antibody known as alpha-2 macrogloblin or α2M reacts with a cell surface receptor called GRP78 which is found on prostate cancer cells.
PSA is a normal product of all prostate cells, at very low levels. When PSA develops and leaks through the cell wall of a prostate cancer cell, however, it can bind to α2M and then the combination of PSA + α2M can form a complex with the GRP78 receptor. It is this complex that activates key pathways which stimulate cancer cell growth and cell movement and block prostate cancer cell death.
If these findings can be replicated, and are shown to be correct, it opens up the possibility that measuring serum levels of α2M alone, of the PSA-α2M combination, and of the PSA-α2M-GRP78 receptor complex may all offer the potential to improve prostate cancer prognosis and monitoring. What is less clear (at least as yet) is whether monitoring levels of these molecules may have significance in determining risk for clinically significant prostate cancer in undiagnosed patients.
It is also the case that this research by Misra et al. could lead to the development of therapies specifically designed to block either the initial development of the PSA-α2M-GRP78 receptor complex or the ability of that complex to stimulate the cell receptor signaling cascade.