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UCLA cancer researchers shake loose hidden biomarker

Using a common chemotherapy agent, researchers at UCLA's Jonsson Cancer Center and the Department of Pathology and Laboratory Medicine found a way to move an important biomarker expressed in prostate cancer, shaking it loose from one location in a cell where it could not be accessed by blood to another, easier to target area.

The discovery, outlined in the cover article of May 11 edition of the peer-reviewed journal Molecular Cancer Therapeutics, could have important implications for using immunotherapy to treat prostate cancer, said Ayyappan K. Rajasekaran, a Jonsson Cancer Center researcher and senior author of the article.

The method discovered by the research team places the prostate-specific membrane antigen (PSMA) in a location on the cell that would allow blood-borne immunotherapies to access the biomarker, transforming it from a hidden target into an exposed one.

"In prostate cancer cells, PSMA is expressed in the apical region of the cell membrane, which blood can't reach, so injection of immunotherapy into the bloodstream is not effective," said Rajasekaran, also an associate professor of pathology and laboratory medicine. "By using information from very basic studies about how the PSMA protein is targeted in these cells, we identified a way to redirect this protein within the cell. We found that if we disturbed hollow tubular structures called microtubules, part of the cell's framework, we were able to relocate PSMA from its 'hidden' location on the apical membrane to an accessible area in the basolateral surface."

To cause this disturbance and the resulting relocation of PSMA, Rajasekaran and his team employed a commonly used cancer chemotherapy agent, which destroys the microtubules.

"These patients are getting chemotherapy anyway, and once we move the PSMA to a more accessible area on the prostate cancer cell, we might be able to use antibody-based immunotherapies as well, and they could be administered in the blood," he sai
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
11-May-2005


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