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Why PSA Levels Reflect Prostate Cancer Progression
"This is the first demonstration of a mechanism that explains why PSA is a bad thing for a tumour to produce," said senior author Sal Pizzo, chair of the Duke Department of Pathology.
"I am willing to bet there is also a connection in cancerous cell growth with this particular biological signalling mechanism happening in other types of cells," he added.
Using human prostate cancer cells in a laboratory culture, the team found that an antibody, called alpha2-macroglobulin (a2M), reacts with a cell surface receptor called GRP78 on the cancer cells to produce more PSA.
The PSA forms a complex with the antibody that also binds to the GRP78 receptor, and that activates several key pathways, which stimulate cancer cell growth and cell movement and block cell death.
The study bolsters the case for measuring PSA as a marker of tumour progression, as well as for monitoring for a2M antibody levels.
"I personally believe PSA is more useful as a progression marker, particularly with a baseline value on record at the time of the original therapy. A rapidly rising value and/or a very high value is reason for concern. I also believe that monitoring the serum for the appearance of antibodies directed against GRP78 is also a good marker of progression," said Pizzo.
He said that the findings could yield cancer therapies that block the a2M-PSA complex from stimulating the cell receptor signalling cascade, and that his laboratory is investigating possibilities.
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