Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures
Abstract
:1. Introduction
2. Results
2.1. Gleason Grade-Dependent Increase in Lactate Concentration and LDHA Expression in Snap-Frozen Patient Biopsies
2.2. 31P Spectroscopy of TSCs: Tissue Viability and Grade-Dependent 31P Spectral Changes
2.3. HP 13C MRS of TSCs: Gleason Grade-Dependent Increases in HP 13C Lactate Signal and Efflux
3. Discussion
4. Materials and Methods
4.1. Quantitative HR-MAS NMR Spectroscopy of Prostate Biopsies
4.2. Prostate Tissue Slice Acquisition and Culture
4.3. 3D Tissue Culture NMR-Compatible Bioreactor
4.4. NMR Spectroscopy Measurements of Prostate TSCs
4.5. Measurement of TSC Lactate Efflux Rate
4.6. Immunohistochemistry (IHC)
4.7. Image Analysis of MCT4 IHC
4.8. Biochemical and Molecular Assays
4.9. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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ID | Age | Pre-op PSA ng/mL | Stage | Gleason Score | % Cancer Cells | % Epithelial Cells | % Stroma |
---|---|---|---|---|---|---|---|
1 | 55 | 5.2 | pT2c pN0 | 3 + 3 | 7 | 37 | 57 |
2 | 53 | 5 | pT2a | 3 + 4 | 53 | 21 | 25 |
3 | 63 | 6.3 | pT2c pN0 | 3 + 4 | 19 | 27 | 54 |
4 | 56 | 7.6 | pT2a | N | -- | 40 | 60 |
5 | 50 | 4.5 | pT2c | N | -- | 40 | 60 |
6 | 65 | 7.1 | pT2c | N | -- | 46 | 53 |
7 | 54 | 6.9 | pT2c | 3 + 4 | 84 | 2 | 15 |
8 | 67 | 3.1 | pT2b | N | -- | 36 | 65 |
9 | 60 | 6.6 | pT2c | N | -- | 45 | 53 |
10 | 71 | 6.9 | pT3b | 3 + 4 | 27 | 36 | 38 |
11 | 71 | 6.9 | pT3b | 4 + 5 | 33 | 36 | 31 |
12 | 55 | 5.4 | pT3a | 4 + 5 | 31 | 29 | 41 |
13 | 55 | 5.4 | pT3a | N | -- | 37 | 63 |
14 | 61 | 6.8 | pT2c | 3 + 4 | 31 | 33 | 36 |
15 | 54 | 4.7 | pT2c | 3 + 4 | 49 | 33 | 19 |
16 | 63 | 4.1 | pT3a | 3 + 4 | 44 | 16 | 41 |
17 | 71 | 5 | pT3b pN0 | 3 + 4 | 11 | 48 | 43 |
18 | 52 | 15.8 | pT3b | 3 + 3 | 26 | 43 | 31 |
19 | 52 | 6.3 | pT3a | 3 + 4 | 20 | 20 | 60 |
20 | 71 | 8.1 | pT3a | 3 + 4 | 48 | 16 | 36 |
21 | 51 | 11.1 | pT3b pN0 | 3 + 3 | 6 | 19 | 74 |
22 | 67 | 4.2 | pT2c | N | -- | 28 | 72 |
23 | 67 | 3.5 | pT2c pN0 | 3 + 4 | 16 | 32 | 52 |
24 | 72 | 5.8 | pT3a | N | -- | 20 | 80 |
25 | 69 | 5 | pT2c | N | -- | 44 | 56 |
26 | 61 | 7.87 | pT2c | 3 + 3 | 42 | 27 | 32 |
27 | 64 | 24.37 | pT3a | 4 + 5 | 40 | 18 | 43 |
30 | 65 | 2.11 | pT3a pN0 | 3 + 4 | 2 | 41 | 58 |
29 | 65 | 2.56 | pT3a | N | -- | 40 | 61 |
31 | 56 | 7.5 | pT2c | N | -- | 34 | 67 |
32 | 56 | 4.5 | pT2c | N | -- | 47 | 53 |
33 | 58 | 13.9 | pT3a pN0 | 3 + 3 | 1 | 34 | 65 |
34 | 66 | 20.6 | pT3b | 4 + 5 | 31 | 8 | 61 |
35 | 69 | 13.8 | pT3b NX | 4 + 4 | 8 | 23 | 68 |
36 | 71 | 7.2 | pT3a | 3 + 4 | 35 | 25 | 40 |
37 | 61 | 5.6 | pT2c | 4 + 3 | 48 | 3 | 51 |
38 | 68 | 8.4 | pT3a pN0 | 3 + 4 | 18 | 33 | 49 |
39 | 71 | 5.9 | pT3a pN0 | 3 + 4 | 11 | 35 | 54 |
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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.; et al. Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures. Cancers 2020, 12, 537. https://doi.org/10.3390/cancers12030537
Sriram R, Van Criekinge M, DeLos Santos J, Ahamed F, Qin H, Nolley R, DeLos Santos R, Tabatabai ZL, Bok RA, Keshari KR, et al. Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures. Cancers. 2020; 12(3):537. https://doi.org/10.3390/cancers12030537
Chicago/Turabian StyleSriram, Renuka, Mark Van Criekinge, Justin DeLos Santos, Fayyaz Ahamed, Hecong Qin, Rosalie Nolley, Romelyn DeLos Santos, Z. Laura Tabatabai, Robert A. Bok, Kayvan R. Keshari, and et al. 2020. "Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures" Cancers 12, no. 3: 537. https://doi.org/10.3390/cancers12030537