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Survey of metabolites finds new prostate cancer marker
Date:2/11/2009

re the levels of 1,126 metabolites in healthy prostate tissue, clinically localized prostate cancer, and metastatic prostate cancer. Sixty metabolites were present in tumor cells, but not in benign tissue. Of these, there were about 10 molecules whose levels increased dramatically during cancer progression. "This is proof-of-principle that we can identify metabolites, or panels of metabolites, that might be correlated with aggressive prostate cancer versus slower-growing prostate cancer," Chinnaiyan said.

Having demonstrated that "metabolomic" profiles change in predictable ways as cancer progresses, the group began more focused analyses. "We began to mine the data to look for metabolites that might serve as biomarkers or as therapeutic targets," Chinnaiyan explained. They chose to focus on sarcosine because it was elevated in clinically localized disease and very highly elevated in metastatic cancer.

They confirmed these dramatic increases in a new set of tissue samples, and also found that there was more sarcosine in the urine of patients with prostate cancer than in healthy individuals.

The team went on to test how sarcosine affected the behavior of cancer cells grown in the laboratory. Adding the chemical to prostate cells or manipulating cells' biochemical pathways so they produced more sarcosine on their own caused benign prostate cells to become cancerous and invasive. Conversely, shutting down sarcosine production in cancer cells blocked invasion.

"This really told us that sarcosine is involved biologically in some of the processes of a cancer cell," Chinnaiyan said. The results suggest that drugs that alter sarcosine metabolism might be useful in treating prostate cancer, but Chinnaiyan cautions that these Petri-dish findings still need further validation in animal models.

An important next step, he says, will be to do similar experiments on the other nine potential biomarkers they identified in this study. F
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
Source:Eurekalert

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