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

Mariantonia Logozzi, Davide Mizzoni, Clemente Capasso, Sonia Del Prete, Rossella Di Raimo, Mario Falchi, Daniela F. Angelini, Alessandro Sciarra, Martina Maggi, Claudiu T. Supuran, Stefano Fais

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)280-288
Number of pages9
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume35
Issue number1
DOIs
Publication statusE-pub ahead of print - Dec 2019

Keywords

  • Acidic tumour microenvironment
  • biomarker
  • carbonic anhydrase IX
  • plasmatic exosomes
  • prostate cancer

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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