In experiments reported in the journal Nature, scientists from the Howard Hughes Medical Institute have identified 10 metabolites that become more profuse in prostate cells as the cancer progresses. They identified one of these metabolites, sarcosine, as appearing to be directly related to prostate cancer cell invasion into surrounding tissue.

We constantly hear the complaint that too many men are over treated for prostate cancer and that the current diagnostic test, the PSA, is over used. The significant underlying problem is that we end up over treating early stage cancers because physicians do not know which tumors will be slow growing and which will be aggressive. They have identified a potential marker for the aggressive tumors claim the senior study author Arul Chinnaiyan, M.D., Ph.D. director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School.

The researchers have demonstrated that as prostate cancer develops and progresses in a man, sarcosine levels increase in both tumor cells and urine samples. This suggests that measuring levels of sarcosine in the urine might also provide a reliable and noninvasive method of determining which cancers are aggressive and in need of treatment and which cancers just need to be monitored. There is an even more exciting possibility that researchers might also be able to inhibit prostate cancer’s spread by designing drugs that manipulate the sarcosine pathway.

The researchers used mass spectrometry, a technique that identifies chemicals based on the size and electrical charge of their components, to compare the levels of 1,126 metabolites in healthy prostate tissue, clinically localized prostate cancer, and metastatic prostate cancer. They found that sixty different metabolites were present in tumor cells, but not in benign tissue. They also observed that about 10 molecules whose levels increased dramatically during prostate cancer progression.

They then demonstrated that “metabolomic” profiles change in predictable ways as cancer progresses so they began a 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 decided to focus on sarcosine because it was elevated in clinically localized disease and very highly elevated in metastatic cancer.

They also found that there was more sarcosine in the urine of patients with prostate cancer than in healthy individuals.

The team then became interested in how sarcosine affected the behavior of cancer cells grown in the laboratory. Adding sarcosine to prostate cells, they found that benign prostate cells to become cancerous and invasive. Conversely, shutting down sarcosine production in cancer cells blocked their invasive nature.

These findings clearly 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 and then in men.

An important next step will be to do similar experiments on the other nine potential biomarkers as well as performing animal experiments with sarcosine. For reliable diagnosis of aggressive disease that will allow us to make better clinical judgments we will need to rely on panels of metabolites, not just rely on a single metabolite.

Sreekumar, A. et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature, February 12, 2009; Vol. 457, No. 7231, pp. 910-915

Joel T Nowak MA, MSW