Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance
Abstract
:1. Introduction
2. pH Heterogeneity in Space
2.1. Protonation as a Post-Translational Modification
2.2. Intracellular pH
2.2.1. Spatial Regulation of Protein Activity via Subcellular pH Heterogeneity
2.2.2. Intercellular pHi Heterogeneity within Tumors
2.3. Extracellular pH
2.3.1. Metabolic and Physiological Contributors to Spatial Gradients and Acidic pHe
2.3.2. Acidic pHe Can Alter Tumor Metabolism
2.3.3. Spatial pHe Gradients Promote Healthy Cell Death, Tumor Aggressiveness, and Therapeutic Resistance
3. pH Heterogeneity in Time
3.1. Carbonic Anhydrase Kinetics
3.2. Effects of pHi Transients on Tumor Cells
3.3. Tumor pHe Decreases Over Time During Tumorigenesis and Disease Progression
4. Techniques to Measure pH Spatiotemporal Heterogeneity
4.1. Fluorescence-Based Measurements
4.2. PET/SPECT-Based Imaging Methods
4.3. MR-Based Techniques
4.3.1. Chemical Exchange Saturation Transfer (CEST)
4.3.2. MR Relaxometry
4.3.3. MR Spectroscopic Approaches
4.3.4. Hyperpolarized (HP) 13C MR Imaging
5. Conclusions
Funding
Conflicts of Interest
References
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Korenchan, D.E.; Flavell, R.R. Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance. Cancers 2019, 11, 1026. https://doi.org/10.3390/cancers11071026
Korenchan DE, Flavell RR. Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance. Cancers. 2019; 11(7):1026. https://doi.org/10.3390/cancers11071026
Chicago/Turabian StyleKorenchan, David E., and Robert R. Flavell. 2019. "Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance" Cancers 11, no. 7: 1026. https://doi.org/10.3390/cancers11071026