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Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy

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posted on 2023-05-20, 11:58 authored by Taylor, J, Iman AzimiIman Azimi, Monteith, G
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.

History

Publication title

Journal of Extracellular Vesicles

Volume

9

Pagination

1-14

ISSN

2001-3078

Department/School

School of Pharmacy and Pharmacology

Publisher

Taylor & Francis

Place of publication

Sweden

Rights statement

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/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified; Expanding knowledge in the biological sciences

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