The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
The Acidic Tumor Microenvironment as a Driver of Cancer
Open accessAbstract
Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Through complex effects on genetic stability, epigenetics, cellular metabolism, proliferation, and survival, the compartmentalized pH microenvironment favors cancer development. Cellular selection exacerbates the malignant phenotype, which is further enhanced by acid-induced cell motility, extracellular matrix degradation, attenuated immune responses, and modified cellular and intercellular signaling. In this review, we discuss how the acidity of the tumor microenvironment influences each stage in cancer development, from dysplasia to full-blown metastatic disease.
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Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926
Cellular Fatty Acid Metabolism and Cancer
Currie, E., Schulze, A., Zechner, R., Walther, T. C., & Farese, R. V. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.017 · Cited by 2,123
Drug Resistance and the Solid Tumor Microenvironment
Tredan, O., Galmarini, C. M., Patel, K., & Tannock, I. F. (2007) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm135 · Cited by 2,116 · cited 1×
“Because the acidic and hypoxic tumor microenvironment facilitates not only malignant development and progression but also treatment resistance (124), the mechanisms that alter tumor vascularization or interfere with tumor vascular function are promising therapeutic targets.”
BackgroundLDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells
Brand, A., Singer, K., Koehl, G. E., Kolitzus, M., Schoenhammer, G., Thiel, A., Matos, C., Bruss, C., Klobuch, S., Peter, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.011 · Cited by 2,039
Biochemistry of exercise-induced metabolic acidosis
Robergs, R. A., Ghiasvand, F., & Parker, D. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00114.2004 · Cited by 1,304
Acid-Mediated Tumor Invasion: a Multidisciplinary Study
Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4193 · Cited by 771
Tumor-derived lactic acid modulates dendritic cell activation and antigen expression
Gottfried, E., Kunz-Schughart, L. A., Ebner, S., Mueller-Klieser, W., Hoves, S., Andreesen, R., Mackensen, A., & Kreutz, M. (2006) · Blood · doi:10.1182/blood-2005-05-1795 · Cited by 729
Calcinotto, A., Filipazzi, P., Grioni, M., Iero, M., De Milito, A., Ricupito, A., Cova, A., Canese, R., Jachetti, E., Rossetti, M., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-1272 · Cited by 640
Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation
Huber, V., Camisaschi, C., Berzi, A., Ferro, S., Lugini, L., Triulzi, T., Tuccitto, A., Tagliabue, E., Castelli, C., & Rivoltini, L. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.03.001 · Cited by 595
Jayaprakash, P., Ai, M., Liu, A., Budhani, P., Bartkowiak, T., Sheng, J., Ager, C., Nicholas, C., Jaiswal, A. R., Sun, Y., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96268 · Cited by 399
Histone Acetylation Regulates Intracellular pH
McBrian, M. A., Behbahan, I. S., Ferrari, R., Su, T., Huang, T.-W., Li, K., Hong, C. S., Christofk, H. R., Vogelauer, M., Seligson, D. B., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.025 · Cited by 272
L-2-Hydroxyglutarate production arises from noncanonical enzyme function at acidic pH
Intlekofer, A. M., Wang, B., Liu, H., Shah, H., Carmona-Fontaine, C., Rustenburg, A. S., Salah, S., Gunner, M. R., Chodera, J. D., Cross, J. R., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2307 · Cited by 268
Corbet, C., Draoui, N., Polet, F., Pinto, A., Drozak, X., Riant, O., & Feron, O. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0705 · Cited by 169
Acidic pH Is a Metabolic Switch for 2-Hydroxyglutarate Generation and Signaling
Nadtochiy, S. M., Schafer, X., Fu, D., Nehrke, K., Munger, J., & Brookes, P. S. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.738799 · Cited by 143
Peppicelli, S., Bianchini, F., Torre, E., & Calorini, L. (2014) · Clinical & Experimental Metastasis · doi:10.1007/s10585-014-9637-6 · Cited by 97
Dovmark, T. H., Saccomano, M., Hulikova, A., Alves, F., & Swietach, P. (2017) · Oncogene · doi:10.1038/onc.2017.71 · Cited by 74
H. Dovmark, T., Hulikova, A., A. Niederer, S., D. Vaughan‐Jones, R., & Swietach, P. (2018) · The FASEB Journal · doi:10.1096/fj.201700480r · Cited by 28
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The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
Lactate metabolism in human health and disease
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01151-3 · Cited by 1,454
The updated landscape of tumor microenvironment and drug repurposing
Jin, M.-Z., & Jin, W.-L. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00280-x · Cited by 1,262
Role of Glutathione in Cancer: From Mechanisms to Therapies
Kennedy, L., Sandhu, J. K., Harper, M.-E., & Cuperlovic-Culf, M. (2020) · Biomolecules · doi:10.3390/biom10101429 · Cited by 880
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Khan, S. U., Fatima, K., Aisha, S., & Malik, F. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01302-1 · Cited by 417
Metadata
- Authors
- Boedtkjer, E., & Pedersen, S. F.
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2020-02-10
- Volume
- 82
- Issue
- 1
- Pages
- 103-126
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2984395468
- Cited by
- 1,223
- References
- 19
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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