The Acidic Tumor Microenvironment as a Driver of Cancer

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 interp...

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Bibliographic Details
Published inAnnual review of physiology Vol. 82; no. 1; pp. 103 - 126
Main Authors Boedtkjer, Ebbe, Pedersen, Stine F
Format Journal Article
LanguageEnglish
Published United States Annual Reviews 10.02.2020
Annual Reviews, Inc
Subjects
Acidity
Cancer
carcinogenesis
Dysplasia
Epigenetics
Extracellular matrix
Immune response
immuno-oncology
Metabolic wastes
Metabolism
Metastases
metastasis
Perfusion
pH effects
Phenotypes
tumor vasculature
Tumors
immuno-oncology
metabolism
acidity
tumor vasculature
carcinogenesis
metastasis
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Summary: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.
ISSN:0066-4278
1545-1585
DOI:10.1146/annurev-physiol-021119-034627