Metabolic Reprogramming and Validation of Hyperpolarized 13C Lactate as a Prostate Cancer Biomarker Using a Human Prostate Tissue Slice Culture Bioreactor. Issue 11 (26th March 2013)

• Record Type: Journal Article
• Authors: Keshari, Kayvan R.; Sriram, Renuka; Van Criekinge, Mark; Wilson, David M.; Wang, Zhen J.; Vigneron, Daniel B.; Peehl, Donna M.; Kurhanewicz, John
• Is Part Of: Prostate. Volume 73:Issue 11(2013)
• Page Start: 1171
• Page End: 1181
• Publication Date: 2013-03-26
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22665
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pros22665-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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) <sup>13</sup>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 <sup>13</sup>C pyruvate MR in a patient‐derived prostate tissue slice culture (TSC) model.</p> </sec> <sec id="pros22665-sec-0002" sec-type="section"> <title>METHODS</title> <p>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 <sup>31</sup>P and HP <sup>13</sup>C MR, respectively.</p> </sec> <sec id="pros22665-sec-0003" sec-type="section"> <title>RESULTS</title> <p>The prostate TSCs demonstrated steady‐state glycolytic and phospholipid metabolism, and bioenergetics that recapitulate features of prostate cancer in vivo. <sup>13</sup>C spectra following injection of HP <sup>13</sup>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).</p> </sec> <sec id="pros22665-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>We provide the first mechanistic evidence for HP <sup>13</sup>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. Prostate 73: 1171–1181, 2013. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>