The Acidic Tumor Microenvironment as a Driver of Cancer

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The Acidic Tumor Microenvironment as a Driver of Cancer. / Boedtkjer, Ebbe; Pedersen, Stine F.

In: Annual Review of Physiology, Vol. 82, 02.2020, p. 103-126.

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Boedtkjer, Ebbe ; Pedersen, Stine F. / The Acidic Tumor Microenvironment as a Driver of Cancer. In: Annual Review of Physiology. 2020 ; Vol. 82. pp. 103-126.

Bibtex

@article{b1ac3f5878694652b31082300c0303f4,
title = "The Acidic Tumor Microenvironment as a Driver of Cancer",
abstract = "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.",
keywords = "acidity, carcinogenesis, immuno-oncology, metabolism, metastasis, tumor vasculature",
author = "Ebbe Boedtkjer and Pedersen, {Stine F.}",
year = "2020",
month = feb,
doi = "10.1146/annurev-physiol-021119-034627",
language = "English",
volume = "82",
pages = "103--126",
journal = "Annual Review of Physiology",
issn = "0066-4278",
publisher = "Annual Reviews",

}

RIS

TY - JOUR

T1 - The Acidic Tumor Microenvironment as a Driver of Cancer

AU - Boedtkjer, Ebbe

AU - Pedersen, Stine F.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - acidity

KW - carcinogenesis

KW - immuno-oncology

KW - metabolism

KW - metastasis

KW - tumor vasculature

UR - http://www.scopus.com/inward/record.url?scp=85078028224&partnerID=8YFLogxK

U2 - 10.1146/annurev-physiol-021119-034627

DO - 10.1146/annurev-physiol-021119-034627

M3 - Review

C2 - 31730395

VL - 82

SP - 103

EP - 126

JO - Annual Review of Physiology

JF - Annual Review of Physiology

SN - 0066-4278

ER -