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Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy

Citation

Taylor, J and Azimi, I and Monteith, G, Ca2+mediates extracellular vesicle biogenesis through alternate pathways in malignancy, Journal of Extracellular Vesicles, 9, (1) pp. 1-14. ISSN 2001-3078 (2020) [Refereed Article]


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DOI: doi:10.1080/20013078.2020.1734326

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.

Item Details

Item Type:Refereed Article
Keywords:Calcium, extracellular vesicle biogenesis, cancer
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmacology and Pharmaceutical Sciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:138070
Year Published:2020
Deposited By:Pharmacy
Deposited On:2020-03-24
Last Modified:2020-03-27
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