Elevated tumor lactate and efflux in high-grade prostate cancer demonstrated by hyperpolarized (13)C magnetic resonance spectroscopy of prostate tissue slice cultures Journal Article
| Authors: | Sriram, R.; Van Criekinge, M.; DeLos Santos, J.; Ahamed, F.; Qin, H.; Nolley, R.; Delos Santos, R.; Tabatabai, Z. L.; Bok, R. A.; Keshari, K. R.; Vigneron, D. B.; Peehl, D. M.; Kurhanewicz, J. |
| Article Title: | Elevated tumor lactate and efflux in high-grade prostate cancer demonstrated by hyperpolarized (13)C magnetic resonance spectroscopy of prostate tissue slice cultures |
| Abstract: | Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP)13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP13C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa. To test this and the ability of HP13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion.31P spectra demonstrated good viability and dynamic HP13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high-versus low-grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. T. |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; protein expression; aged; middle aged; unclassified drug; cancer grading; cell viability; gene expression; image analysis; enzyme activity; high risk patient; risk assessment; prostate cancer; gleason score; prostate biopsy; tracer; tissue level; phosphorus 31; carbon nuclear magnetic resonance; lactic acid; pyruvic acid; low risk patient; aerobic glycolysis; benign neoplasm; tissue metabolism; human; male; article; lactate dehydrogenase a; dynamic nuclear polarization (dnp); lactate efflux; monocarboxylate transporter 4; prostate tissue; ldha gene; hyperpolarized13c magnetic resonance (hp13c mr); lactate dehydrogenase (ldh); pyruvate c 13; slice culture |
| Journal Title: | Cancers |
| Volume: | 12 |
| Issue: | 3 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2020-03-01 |
| Start Page: | 537 |
| Language: | English |
| DOI: | 10.3390/cancers12030537 |
| PROVIDER: | scopus |
| PUBMED: | 32110965 |
| PMCID: | PMC7139946 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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