How Reciprocal Interactions Between the Tumor Microenvironment and Ion Transport Proteins Drive Cancer Progression
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How Reciprocal Interactions Between the Tumor Microenvironment and Ion Transport Proteins Drive Cancer Progression. / Elingaard-Larsen, Line O.; Rolver, Michala G.; Sørensen, Ester E.; Pedersen, Stine F.
From Malignant Transformation to Metastasis: Ion Transport in Tumor Biology. ed. / Christian Stock; Luis A. Pardo. Springer, 2022. p. 1-38 (Reviews of Physiology, Biochemistry and Pharmacology, Vol. 182).Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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TY - CHAP
T1 - How Reciprocal Interactions Between the Tumor Microenvironment and Ion Transport Proteins Drive Cancer Progression
AU - Elingaard-Larsen, Line O.
AU - Rolver, Michala G.
AU - Sørensen, Ester E.
AU - Pedersen, Stine F.
N1 - Publisher Copyright: © 2020, Springer Nature Switzerland AG.
PY - 2022
Y1 - 2022
N2 - Solid tumors comprise two major components: the cancer cells and the tumor stroma. The stroma is a mixture of cellular and acellular components including fibroblasts, mesenchymal and cancer stem cells, endothelial cells, immune cells, extracellular matrix, and tumor interstitial fluid. The insufficient tumor perfusion and the highly proliferative state and dysregulated metabolism of the cancer cells collectively create a physicochemical microenvironment characterized by altered nutrient concentrations and varying degrees of hypoxia and acidosis. Furthermore, both cancer and stromal cells secrete numerous growth factors, cytokines, and extracellular matrix proteins which further shape the tumor microenvironment (TME), favoring cancer progression. Transport proteins expressed by cancer and stromal cells localize at the interface between the cells and the TME and are in a reciprocal relationship with it, as both sensors and modulators of TME properties. It has been amply demonstrated how acid-base and nutrient transporters of cancer cells enable their growth, presumably by contributing both to the extracellular acidosis and the exchange of metabolic substrates and waste products between cells and TME. However, the TME also impacts other transport proteins important for cancer progression, such as multidrug resistance proteins. In this review, we summarize current knowledge of the cellular and acellular components of solid tumors and their interrelationship with key ion transport proteins. We focus in particular on acid-base transport proteins with known or proposed roles in cancer development, and we discuss their relevance for novel therapeutic strategies.
AB - Solid tumors comprise two major components: the cancer cells and the tumor stroma. The stroma is a mixture of cellular and acellular components including fibroblasts, mesenchymal and cancer stem cells, endothelial cells, immune cells, extracellular matrix, and tumor interstitial fluid. The insufficient tumor perfusion and the highly proliferative state and dysregulated metabolism of the cancer cells collectively create a physicochemical microenvironment characterized by altered nutrient concentrations and varying degrees of hypoxia and acidosis. Furthermore, both cancer and stromal cells secrete numerous growth factors, cytokines, and extracellular matrix proteins which further shape the tumor microenvironment (TME), favoring cancer progression. Transport proteins expressed by cancer and stromal cells localize at the interface between the cells and the TME and are in a reciprocal relationship with it, as both sensors and modulators of TME properties. It has been amply demonstrated how acid-base and nutrient transporters of cancer cells enable their growth, presumably by contributing both to the extracellular acidosis and the exchange of metabolic substrates and waste products between cells and TME. However, the TME also impacts other transport proteins important for cancer progression, such as multidrug resistance proteins. In this review, we summarize current knowledge of the cellular and acellular components of solid tumors and their interrelationship with key ion transport proteins. We focus in particular on acid-base transport proteins with known or proposed roles in cancer development, and we discuss their relevance for novel therapeutic strategies.
KW - Acidosis
KW - Hypoxia
KW - Lactate
KW - Monocarboxylate transporters
KW - Na/H exchange
KW - Na/HCO cotransport
KW - pH regulatory transporters
KW - Tumor heterogeneity
KW - Tumor stroma
KW - V-type ATPases
U2 - 10.1007/112_2020_23
DO - 10.1007/112_2020_23
M3 - Book chapter
C2 - 32737753
AN - SCOPUS:85129168408
SN - 978-3-030-99799-1
T3 - Reviews of Physiology, Biochemistry and Pharmacology
SP - 1
EP - 38
BT - From Malignant Transformation to Metastasis
A2 - Stock, Christian
A2 - Pardo, Luis A.
PB - Springer
ER -
ID: 310419495