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The role of sarcosine metabolism in prostate cancer progression.
The role of sarcosine metabolism in prostate cancer progression.
- Source :
-
Neoplasia (New York, N.Y.) [Neoplasia] 2013 May; Vol. 15 (5), pp. 491-501. - Publication Year :
- 2013
-
Abstract
- Metabolomic profiling of prostate cancer (PCa) progression identified markedly elevated levels of sarcosine (N-methyl glycine) in metastatic PCa and modest but significant elevation of the metabolite in PCa urine. Here, we examine the role of key enzymes associated with sarcosine metabolism in PCa progression. Consistent with our earlier report, sarcosine levels were significantly elevated in PCa urine sediments compared to controls, with a modest area under the receiver operating characteristic curve of 0.71. In addition, the expression of sarcosine biosynthetic enzyme, glycine N-methyltransferase (GNMT), was elevated in PCa tissues, while sarcosine dehydrogenase (SARDH) and pipecolic acid oxidase (PIPOX), which metabolize sarcosine, were reduced in prostate tumors. Consistent with this, GNMT promoted the oncogenic potential of prostate cells by facilitating sarcosine production, while SARDH and PIPOX reduced the oncogenic potential of prostate cells by metabolizing sarcosine. Accordingly, addition of sarcosine, but not glycine or alanine, induced invasion and intravasation in an in vivo PCa model. In contrast, GNMT knockdown or SARDH overexpression in PCa xenografts inhibited tumor growth. Taken together, these studies substantiate the role of sarcosine in PCa progression.
- Subjects :
- Aged
Animals
Case-Control Studies
Cell Line, Tumor
Disease Progression
Gene Expression
Gene Expression Regulation, Neoplastic
Glycine N-Methyltransferase genetics
Glycine N-Methyltransferase metabolism
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Prostatic Neoplasms enzymology
Prostatic Neoplasms pathology
Sarcosine Dehydrogenase genetics
Sarcosine Dehydrogenase metabolism
Sarcosine Oxidase genetics
Sarcosine Oxidase metabolism
Tumor Burden
Biomarkers, Tumor urine
Prostatic Neoplasms urine
Sarcosine urine
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5586
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neoplasia (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 23633921
- Full Text :
- https://doi.org/10.1593/neo.13314