BACKGROUND: The treatment of prostate cancer has been impeded by the lack of both clinically relevant disease models and metabolic markers that track tumor progression.
Hyperpolarized (HP) 13 C MR spectroscopy has emerged as a new technology to investigate the metabolic shifts in prostate cancer. In this study, we investigate the glucose reprogramming using HP 13 C pyruvate MR in a patient-derived prostate tissue slice culture (TSC) model.
METHODS: The steady-state metabolite concentrations in freshly excised human prostate TSCs were assessed and compared to those from snap-frozen biopsy samples. The TSCs were then applied to a perfused cell (bioreactor) platform, and the bioenergetics and the dynamic pyruvate flux of the TSCs were investigated by 31 P and HP 13 C MR, respectively.
RESULTS: The prostate TSCs demonstrated steady-state glycolytic and phospholipid metabolism, and bioenergetics that recapitulate features of prostate cancer in vivo. 13 C spectra following injection of HP 13 C pyruvate showed significantly increased pyruvate to lactate flux in malignant as compared to the benign prostate TSCs. This increased flux in the malignant prostate TSCs correlated with both increased expression of monocarboxylate transporters (MCT) and activity of lactate dehydrogenase (LDH).
CONCLUSIONS: We provide the first mechanistic evidence for HP 13 C lactate as a prostate cancer biomarker in living human tissues, critical for the interpretation of in vivo studies. More broadly, the clinically relevant metabolic model system in combination with HP MR can facilitate the identification of clinically translatable biomarkers of prostate cancer presence, aggressiveness, and treatment response.
Written by:
Keshari KR, Sriram R, Van Criekinge M, Wilson DM, Wang ZJ, Vigneron DB, Peehl DM, Kurhanewicz J. Are you the author?
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
Reference: Prostate. 2013 Mar 26. Epub ahead of print.
doi: 10.1002/pros.22665
PubMed Abstract
PMID: 23532911
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