Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

A prostate cancer marker A systematic analysis of metabolites in prostate cancer samples has led to the discovery that sarcosine, an amino acid common in many biological tissues including muscle, is highly elevated in aggressive prostate cancers and detectable in the urine of men with prostate cancer. This makes sarcosine a candidate biomarker for prostate cancer diagnosis. Targeted knockdown of the enzyme that generates sarcosine from glycine attenuated prostate cell invasion in mice, pointing to a possible role in metastasis, and adding the sarcosine pathway to the list of possible therapeutic targets. A systematic analysis of metabolites in prostate cancer samples has led to the identification of sarcosine as a putative biomarker detectable in urine, which could potentially be used to aid prostate cancer diagnosis. Sarcosine promotes the invasion of prostate cancer cells and may play a role in metastasis. Multiple, complex molecular events characterize cancer development and progression 1 , 2 . Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N -methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. 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. Androgen receptor and the ERG gene fusion product coordina