sarcosine in prostate cancer

February 11, 2009

Potential role for sarcosine in prostate cancer progression

A very interesting paper in Nature this week looked at a metabolite called sarcosine and how it's detection in urine may distinguish slow growing prostate cancers from aggressive ones. The paper, entitled "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression", may well be a useful new marker in helping doctors decide when to stop 'watchful waiting' and treat prostate cancer patients more aggressively.

The researchers examined 1,126 metabolites from over 260 samples of blood, urine and tissue in benign prostate tissue, early stage prostate cancer and advanced or metastatic disease to enable them to map alterations in disease state.

Sarcosine molecule from: jchemed.chem.wisc.edu

They found 10 that were present more often in prostate cancer samples and one, sarcosine, appeared to offer the strongest indicator.

"... by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity."

Sarcosine is an amino acid and was found to be elevated in 79% of the metastatic prostate cancer samples and 42% of the early prostate cancer samples. None of the cancer-free samples had detectable levels of the metabolite.

So how does this happen? Is there an explanation for the phenomenon reported? The researchers went on to say that:

"Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway."

What was also interesting was the finding that:

"Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells."

In other words, they found a clear relationship between the sarcosine and the metastatic invasion. The study also found that sarcosine was a better indicator of advancing disease than the traditional measure, prostate specific antigen (PSA), which is currently used to monitor prostate cancer.

Sources:

Thanks to Prof Chris Beecher for kindly supplying a copy of the Nature reprint.

Arun Sreekumar, Laila M. Poisson, Thekkelnaycke M. Rajendiran, Amjad P. Khan, Qi Cao, Jindan Yu, Bharathi Laxman, Rohit Mehra, Robert J. Lonigro, Yong Li, Mukesh K. Nyati, Aarif Ahsan, Shanker Kalyana-Sundaram, Bo Han, Xuhong Cao, Jaeman Byun, Gilbert S. Omenn, Debashis Ghosh, Subramaniam Pennathur, Danny C. Alexander, Alvin Berger, Jeffrey R. Shuster, John T. Wei, Sooryanarayana Varambally, Christopher Beecher, Arul M. Chinnaiyan (2009). Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature, 457 (7231), 910-914 DOI: 10.1038/nature07762