Plasmatic exosomes from prostate cancer patients show increased carbonic anhydrase IX expression and activity and low pH |
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Authors: | Mariantonia Logozzi Davide Mizzoni Clemente Capasso Sonia Del Prete Rossella Di Raimo Mario Falchi |
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Institution: | 1. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy mariantonia.logozzi@iss.it;3. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy;4. National Research Council, Institute of Biosciences and BioResources, Naples, Italy https://orcid.org/0000-0003-3314-2411;5. National Research Council, Institute of Biosciences and BioResources, Naples, Italy;6. National AIDS Center, Istituto Superiore di Sanità, Rome, Italy |
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Abstract: | 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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Keywords: | Acidic tumour microenvironment prostate cancer carbonic anhydrase IX plasmatic exosomes biomarker |
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