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Researchers learn why PSA levels reflect prostate cancer progression
Date:1/13/2011

DURHAM, N.C. Researchers at the Duke Cancer Institute who have been studying prostate cancer cells for decades now think they know why PSA (prostate-specific antigen) levels reflect cancer progression.

"This is the first demonstration of a mechanism that explains why PSA is a bad thing for a tumor to produce," said senior author Sal Pizzo, M.D., Ph.D., 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 signaling mechanism happening in other types of cells."

Using human prostate cancer cells in a laboratory culture, the team found that an antibody reacts with a cell surface receptor called GRP78 on the cancer cells to produce more PSA. The PSA arises inside of the cancer cell and then moves outside of the cell, where it can bind with the same antibody, called alpha2-macroglobulin (α2M).

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 tumor progression, as well as for monitoring for α2M antibody levels.

"The use of PSA to make the initial diagnosis of prostate cancer has become controversial over the past decade," Pizzo said. "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."

Pizzo said that the findings could yield cancer therapies that block the α2M-PSA complex from stimulating the cell receptor signaling cascade, and that his laboratory is investigating possibilities. He said the findings al
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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