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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Prostate cancer (PCa) pathogenesis relies on intercellular communication, which can involve tunnelling nanotubes (TNTs) and extracellular vesicles (EVs). TNTs and EVs have been reported to transfer critical cargo involved in cellular functions and signalling, prompting us to investigate the extent of organelle and protein transfer in PCa cells and the potential involvement of the androgen receptor. Using live cell imaging microscopy, we observed extensive formation of TNTs and EVs operating between PCa, non-malignant, and immune cells. PCa cells were capable of transferring lysosomes, mitochondria, lipids, and endoplasmic reticulum, as well as syndecan-1, sortilin, Glut1, and Glut4. In mechanistic studies, androgen-sensitive PCa cells exhibited changes in cell morphology when stimulated by R1881 treatment. Overexpression assays of a newly designed androgen receptor (AR) plasmid revealed its novel localization in PCa cellular vesicles, which were also transferred to neighbouring cells. Selected molecular machinery, thought to be involved in intercellular communication, was investigated by knockdown studies and Western blotting/immunofluorescence/scanning electron microscopy (SEM). PCa TNTs and EVs transported proteins and organelles, which may contain specialist signalling, programming, and energy requirements that support cancer growth and progression. This makes these important intercellular communication systems ideal potential targets for therapeutic intervention.

Details

Title
Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication
Author
Heatlie, Jessica K 1   VIAFID ORCID Logo  ; Lazniewska, Joanna 1 ; Moore, Courtney R 1   VIAFID ORCID Logo  ; Johnson, Ian R D 1   VIAFID ORCID Logo  ; Nturubika, Bukuru D 1   VIAFID ORCID Logo  ; Williams, Ruth 1   VIAFID ORCID Logo  ; Ward, Mark P 2   VIAFID ORCID Logo  ; John J O’Leary 2   VIAFID ORCID Logo  ; Butler, Lisa M 3   VIAFID ORCID Logo  ; Brooks, Doug A 4   VIAFID ORCID Logo 

 Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia 
 Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland 
 South Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA 5005, Australia; Solid Tumour Program, Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia 
 Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia; Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland 
First page
23
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
2218273X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3159417774
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.