High serum carbonic anhydrase IX predicts shorter survival in head and neck cancer

Rosenberg,; Pastorekova, S; Zaťovičová, Miriam; Vidličková, Ivana; Jelenska, Lenka; Slezák, Peter

doi:10.4149/bll_2016_038

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…As hypoxic tumors are a known source of sCAIX [25][26][27] , we assessed cancer prevalence. The presence of cancer could not have influenced our data, since 17 (3.5%) participants with undetectable sCAIX reported active cancer, compared to 3 participants with detectable levels (3.8%).…”

Section: Resultsmentioning

confidence: 99%

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The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease

Demandt

Dubois²,

Kuijk

et al. 2021

Sci Rep

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Hypoxia is prevalent in atherosclerotic plaques, promoting plaque aggravation and subsequent cardiovascular disease (CVD). Transmembrane protein carbonic anhydrase IX (CAIX) is hypoxia-induced and can be shed into the circulation as soluble CAIX (sCAIX). As plaque macrophages are hypoxic, we hypothesized a role for CAIX in macrophage function, and as biomarker of hypoxic plaque burden and CVD. As tumor patients with probable CVD are treated with CAIX inhibitors, this study will shed light on their safety profile. CAIX co-localized with macrophages (CD68) and hypoxia (pimonidazole), and correlated with lipid core size and pro-inflammatory iNOS+ macrophages in unstable human carotid artery plaques. Although elevated pH and reduced lactate levels in culture medium of CAIX knock-out (CAIXko) macrophages confirmed its role as pH-regulator, only spare respiratory capacity of CAIXko macrophages was reduced. Proliferation, apoptosis, lipid uptake and expression of pro- and anti-inflammatory genes were not altered. Plasma sCAIX levels and plaque-resident CAIX were below the detection threshold in 50 and 90% of asymptomatic and symptomatic cases, respectively, while detectable levels did not associate with primary or secondary events, or intraplaque hemorrhage. Initial findings show that CAIX deficiency interferes with macrophage metabolism. Despite a correlation with inflammatory macrophages, plaque-resident and sCAIX expression levels are too low to serve as biomarkers of future CVD.

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Section: Resultsmentioning

confidence: 99%

“…After washing, 100 µl of detection antibody (200 ng/ml) were added and incubated for 2 h at RT; streptavidin-HRP (100 µl) was used as a detector. Reaction was stopped by adding 50 µl of the stop solution and the optical density of each well was determined using a microplate reader set to 492 nm 25 .…”

Section: Methodsmentioning

confidence: 99%

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease

Demandt

Dubois²,

Kuijk

et al. 2021

Sci Rep

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“…TACE/ADAM17 has been found to induce the shedding of the extracellular domain of CAIX, also called soluble CAIX [101] . This molecule has been detected in the sera of cancer patients and has been shown diagnostic and/or prognostic in several cancers, including head and neck cancer [102] , breast cancer, prostate cancer [103] , renal cell carcinoma [104] , [105] , [106] , ovarian cancer [107] , gastric cancer [108] , rectal cancer [109] , and non-small cell lung cancer [103] , [110] .…”

Section: Acidic Metabolitesmentioning

confidence: 99%

Cancer metabolism: New insights into classic characteristics

Kato

Maeda

Suzuki

et al. 2018

Japanese Dental Science Review

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SummaryInitial studies of cancer metabolism in the early 1920s found that cancer cells were phenotypically characterized by aerobic glycolysis, in that these cells favor glucose uptake and lactate production, even in the presence of oxygen. This property, called the Warburg effect, is considered a hallmark of cancer. The mechanism by which these cells acquire aerobic glycolysis has been uncovered. Acidic extracellular fluid, secreted by cancer cells, induces a malignant phenotype, including invasion and metastasis. Cancer cells survival depends on a critical balance of redox status, which is regulated by amino acid metabolism. Glutamine is extremely important for oxidative phosphorylation and redox regulation. Cells highly dependent on glutamine and that cannot survive with glutamine are called glutamine-addicted cells. Metabolic reprogramming has been observed in cancer stem cells, which have the property of self-renewal and are resistant to chemotherapy and radiotherapy. These findings suggest that studies of cancer metabolism can reveal methods of preventing cancer recurrence and metastasis.

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“…CA IX is a zinc metalloenzyme belonging to a broader group of 15 isoforms involved in the catalysis of carbon dioxide hydration to bicarbonate and proton. Among these isoforms, CA IX has high clinical relevance in cancer therapy since it is implicated in tumorigenesis 13,31,32 and considered a marker of tumour hypoxia [33][34][35][36] . CA IX is overexpressed in a large number of solid tumours, whereas its expression in normal tissues is quite limited, suggesting its role as valuable tumour biomarker.…”

Section: Introductionmentioning

confidence: 99%

Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH

Logozzi

Mizzoni

Capasso

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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2020) Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH, Journal of Enzyme Inhibition and Medicinal Chemistry, 35:1, 280-288, ABSTRACT Acidity, hypoxia and increased release of exosomes are severe phenotypes of tumours. The regulation of pH in tumours involves the interaction of several proteins, including the carbonic anhydrases which catalyze the formation of bicarbonate and protons from carbon dioxide and water. Among CA isoforms, CA IX is over-expressed in a large number of solid tumours, conferring to cancer cells a survival advantage in hypoxic and acidic microenvironment, but there isn't evidence that CA IX expression could have a real clinical impact. Therefore, in this study for the first time the expression and activity of CA IX have been investigated in the plasmatic exosomes obtained from patients with prostate carcinoma (PCa). For this purpose, the study was performed through different methodological approaches, such as NTA, western blot analysis, enzyme activity assay, Nanoscale flow cytometry, ELISA, confocal microscopy. The results showed that PCa exosomes significantly overexpressed CA IX levels and related activity as compared to healthy donors. Furthermore, CA IX expression and activity were correlated to the exosome intraluminal pH, demonstrating for the first time that PCa exosomes are acidic. Our data suggest the possible use of the exosomal CA IX expression and activity as a biomarker of cancer progression in PCa.

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High serum carbonic anhydrase IX predicts shorter survival in head and neck cancer

Cited by 5 publications

References 14 publications

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease

The hypoxia-sensor carbonic anhydrase IX affects macrophage metabolism, but is not a suitable biomarker for human cardiovascular disease

Cancer metabolism: New insights into classic characteristics

Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH

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