The Acidic Tumor Microenvironment as a Driver of Cancer
Autor: | Ebbe Boedtkjer, Stine F. Pedersen |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Stromal cell Physiology medicine.disease_cause Metastasis Extracellular matrix 03 medical and health sciences 0302 clinical medicine Neoplasms medicine Extracellular Tumor Microenvironment Animals Humans metastasis Neoplasm Metastasis acidity immuno-oncology Tumor microenvironment Chemistry Cancer Hydrogen-Ion Concentration medicine.disease Cell biology tumor vasculature 030104 developmental biology 030220 oncology & carcinogenesis Carcinogenesis Extracellular Matrix Degradation Acids carcinogenesis metabolism Signal Transduction |
Zdroj: | Boedtkjer, E & Pedersen, S F 2020, ' The Acidic Tumor Microenvironment as a Driver of Cancer ', Annual Review of Physiology, vol. 82, pp. 103-126 . https://doi.org/10.1146/annurev-physiol-021119-034627 |
Popis: | 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. |
Databáze: | OpenAIRE |
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