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Published in: Cancer and Metastasis Reviews 4/2021

Open Access 01-12-2021 | Acidosis

Understanding metabolic alterations and heterogeneity in cancer progression through validated immunodetection of key molecular components: a case of carbonic anhydrase IX

Authors: Martina Takacova, Ivana Kajanova, Maria Kolarcikova, Jana Lapinova, Miriam Zatovicova, Silvia Pastorekova

Published in: Cancer and Metastasis Reviews | Issue 4/2021

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Abstract

Cancer metabolic heterogeneity develops in response to both intrinsic factors (mutations leading to activation of oncogenic pathways) and extrinsic factors (physiological and molecular signals from the extracellular milieu). Here we review causes and consequences of metabolic alterations in cancer cells with focus on hypoxia and acidosis, and with particular attention to carbonic anhydrase IX (CA IX). CA IX is a cancer-associated enzyme induced and activated by hypoxia in a broad range of tumor types, where it participates in pH regulation as well as in molecular mechanisms supporting cancer cells’ invasion and metastasis. CA IX catalyzes reversible conversion of carbon dioxide to bicarbonate ion plus proton and cooperates with a spectrum of molecules transporting ions or metabolites across the plasma membrane. Thereby CA IX contributes to extracellular acidosis as well as to buffering intracellular pH, which is essential for cell survival, metabolic performance, and proliferation of cancer cells. Since CA IX expression pattern reflects gradients of oxygen, pH, and other intratumoral factors, we use it as a paradigm to discuss an impact of antibody quality and research material on investigating metabolic reprogramming of tumor tissue. Based on the validation, we propose the most reliable CA IX-specific antibodies and suggest conditions for faithful immunohistochemical analysis of molecules contributing to heterogeneity in cancer progression.
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Metadata
Title
Understanding metabolic alterations and heterogeneity in cancer progression through validated immunodetection of key molecular components: a case of carbonic anhydrase IX
Authors
Martina Takacova
Ivana Kajanova
Maria Kolarcikova
Jana Lapinova
Miriam Zatovicova
Silvia Pastorekova
Publication date
01-12-2021
Publisher
Springer US
Keyword
Acidosis
Published in
Cancer and Metastasis Reviews / Issue 4/2021
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-021-10011-5

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