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Energy-requiring uptake of prostasomes and PC3 cell-derived exosomes into non-malignant and malignant cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
Department of Oncology-Pathology, Karolinska Institutet and University Hospital, Stockholm, Sweden..
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2016 (English)In: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 5, 29877Article in journal (Refereed) Published
Abstract [en]

Epithelial cells lining the prostate acini release, in a regulated manner (exocytosis), nanosized vesicles called prostasomes that belong to the exosome family. Prostate cancer cells have preserved this ability to generate and export exosomes to the extracellular space. We previously demonstrated that human prostasomes have an ATP-forming capacity. In this study, we compared the capacity of extracellular vesicles (EVs) to generate ATP between normal seminal prostasomes and exosomes secreted by PC3 cells (PC3 exosomes), a prostate cancer cell line. Proteomic analyses identified enzymes of the glycolytic chain in both prostasomes and PC3 exosomes, and we found that both of them were capable of generating ATP when supplied with substrates. Notably, the net production of extracellular ATP was low for prostasomes due to a high ATPase activity contrary to an elevated net ATP level for PC3 exosomes because of their low ATPase activity. The uptake of the 2 types of EVs by normal prostate epithelial cells (CRL2221) and prostate cancer cells (PC3) was visualized and measured, demonstrating differential kinetics. Interestingly, this uptake was dependent upon an ongoing glycolytic flux involving extracellular ATP formation by EVs and/or intracellular ATP produced from the recipient cells. We conclude that the internalization of EVs into recipient cells is an energy-requiring process also demanding an active V-ATPase and the capacity of EVs to generate extracellular ATP may play a role in this process.

Place, publisher, year, edition, pages
2016. Vol. 5, 29877
Keyword [en]
extracellular ATP; prostate cancer; extracellular vesicles; exosomes; prostasomes; ATPase; glycolysis; energy metabolism; exosome uptake
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-281232DOI: 10.3402/jev.v5.29877ISI: 000375921700001PubMedID: 26955882OAI: oai:DiVA.org:uu-281232DiVA: diva2:913356
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-11-30Bibliographically approved

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