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news.In a discovery that could pave the way for immunotherapies, researchers at UCLA's Jonsson Cancer Center and the Department of Pathology and Laboratory Medicine have found a way to move shake lose an important biomarker expressed in prostate cancer, moving it to an easier to target area.
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The discovery, outlined in an article in the journal Molecular Cancer Therapeutics, could have important implications for using immunotherapy to treat prostate cancer, according to Ayyappan 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. “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.
The researchers also showed for the first time in this study that prostate cancer cells maintain a well-differentiated morphology, with the PSMA hidden in the apical membrane of the cell, even when the cancer spreads outside the prostate – a fact that hadn’t been proven before. This means that moving the PSMA to a more treatment-accessible location on the cell could have ramifications for treating the most ill patients, those in whom the cancer has spread.
The researchers plan to validate their findings first in animal models and then in human clinical trials, which could be available in three to four years.