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Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy

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Taylor, J, Azimi, I ORCID: 0000-0001-9477-9999 and Monteith, G 2020 , 'Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy' , Journal of Extracellular Vesicles, vol. 9, no. 1 , pp. 1-14 , doi: 10.1080/20013078.2020.1734326.

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Abstract

Extracellular vesicles (EVs) are small extracellular membrane vesicles that serve as important intercellular signalling intermediaries in both malignant and non-malignant cells. For EVs formed by theplasma membrane, their biogenesis is characterized by an increase in intracellular calcium followedby successive membrane and cytoskeletal changes. EV production is significantly higher in malignantcells relative to non-malignant cells and previous work suggests this is dependent on increasedcalcium mobilization and activity of calpain. However, differences in calcium-signalling pathways inthe context of malignant and non-malignant EV biogenesis remain unexplored. Here, we demonstrate vesiculation is greater in malignant MCF-7 cells relative to non-malignant hCMEC-D3 cells,increases in free cytosolic Ca2+via endoplasmic reticulum (ER) Ca2+ store depletion with thapsigarginincreases EV biogenesis in both cell types, and vesicular induction is abolished by the intracellular Ca2+ chelator BAPTA-AM. Store-operated calcium entry (SOCE) plays an essential role in the maintenanceof EV biogenesis after store depletion. These findings contribute to furthering our understanding ofextracellular vesicle biogenesis. Furthermore, since EVs are key mediators in the intercellular transferof deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecularmechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutictargets that circumvent EV-mediated MDR.

Item Type: Article
Authors/Creators:Taylor, J and Azimi, I and Monteith, G
Keywords: Calcium, extracellular vesicle biogenesis, cancer
Journal or Publication Title: Journal of Extracellular Vesicles
Publisher: Taylor & Francis
ISSN: 2001-3078
DOI / ID Number: 10.1080/20013078.2020.1734326
Copyright Information:

Copyright 2020 The Authors. Licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/

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