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

Abstract

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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Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

“…Notably, preclinical studies have shown that exosomes are able to shuttle different kinds of molecules, including chemotherapeutics [136], drugs possibly useful to work as both effective molecules and tracers, representing a prototype for "Theranostics" [137,138], but nanoparticles as well [139], thus really supporting their exploitation as a natural delivery system for both diagnostics and therapeutics [140,141]. Moreover, their structure allows them to deliver active molecules as well, and this has been shown in in vitro models [142], and in vivo as well [143]. Lastly, it has been shown that exosome release and size are profoundly changed by extracellular acidity [144], suggesting that when using EVs or exosomes as a delivery system for the treatment of cancers the source of these should always be chosen very carefully [7] (Table 1).…”

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