Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy.

Taylor, J; Azimi, I; Monteith, G; Bebawy, M

Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy.

Taylor, J Azimi, I Monteith, G Bebawy, M

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Publisher:: TAYLOR & FRANCIS LTD
Publication Type:: Journal Article
Citation:: Journal of extracellular vesicles, 2020, 9, (1)
Issue Date:: 2020-01

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Field	Value	Language
dc.contributor.author	Taylor, J
dc.contributor.author	Azimi, I
dc.contributor.author	Monteith, G
dc.contributor.author	Bebawy, M https://orcid.org/0000-0003-2606-921X
dc.date.accessioned	2020-07-31T04:42:23Z
dc.date.available	2020-02-11
dc.date.available	2020-07-31T04:42:23Z
dc.date.issued	2020-01
dc.identifier.citation	Journal of extracellular vesicles, 2020, 9, (1)
dc.identifier.issn	2001-3078
dc.identifier.issn	2001-3078
dc.identifier.uri	http://hdl.handle.net/10453/141947
dc.description.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 the plasma membrane, their biogenesis is characterized by an increase in intracellular calcium followed by successive membrane and cytoskeletal changes. EV production is significantly higher in malignant cells relative to non-malignant cells and previous work suggests this is dependent on increased calcium mobilization and activity of calpain. However, differences in calcium-signalling pathways in the 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 thapsigargin increases 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 maintenance of EV biogenesis after store depletion. These findings contribute to furthering our understanding of extracellular vesicle biogenesis. Furthermore, since EVs are key mediators in the intercellular transfer of deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecular mechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutic targets that circumvent EV-mediated MDR.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	TAYLOR & FRANCIS LTD
dc.relation.ispartof	Journal of extracellular vesicles
dc.relation.isbasedon	10.1080/20013078.2020.1734326
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), whichpermits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subject	0601 Biochemistry and Cell Biology
dc.title	Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy.
dc.type	Journal Article
utslib.citation.volume	9
utslib.location.activity	Sweden
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health/GSH.Pharmacy
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Graduate School of Health
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-07-31T04:42:13Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	9
utslib.citation.issue	1

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 the plasma membrane, their biogenesis is characterized by an increase in intracellular calcium followed by successive membrane and cytoskeletal changes. EV production is significantly higher in malignant cells relative to non-malignant cells and previous work suggests this is dependent on increased calcium mobilization and activity of calpain. However, differences in calcium-signalling pathways in the 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 thapsigargin increases 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 maintenance of EV biogenesis after store depletion. These findings contribute to furthering our understanding of extracellular vesicle biogenesis. Furthermore, since EVs are key mediators in the intercellular transfer of deleterious cancer traits such as cancer multidrug resistance (MDR), understanding the molecular mechanisms governing their biogenesis in cancer is the crucial first step in finding novel therapeutic targets that circumvent EV-mediated MDR.

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http://hdl.handle.net/10453/141947