Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication
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 o...
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2024-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/15/1/23 |
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| author | Jessica K. Heatlie Joanna Lazniewska Courtney R. Moore Ian R. D. Johnson Bukuru D. Nturubika Ruth Williams Mark P. Ward John J. O’Leary Lisa M. Butler Doug A. Brooks |
| author_facet | Jessica K. Heatlie Joanna Lazniewska Courtney R. Moore Ian R. D. Johnson Bukuru D. Nturubika Ruth Williams Mark P. Ward John J. O’Leary Lisa M. Butler Doug A. Brooks |
| author_sort | Jessica K. Heatlie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3eeaf235383c4930ab108265060ae00d |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-3eeaf235383c4930ab108265060ae00d2025-01-24T13:24:53ZengMDPI AGBiomolecules2218-273X2024-12-011512310.3390/biom15010023Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular CommunicationJessica K. Heatlie0Joanna Lazniewska1Courtney R. Moore2Ian R. D. Johnson3Bukuru D. Nturubika4Ruth Williams5Mark P. Ward6John J. O’Leary7Lisa M. Butler8Doug A. Brooks9Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaDepartment of Histopathology, Trinity College Dublin, D02 PN40 Dublin, IrelandDepartment of Histopathology, Trinity College Dublin, D02 PN40 Dublin, IrelandSouth Australian ImmunoGENomics Cancer Institute and Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, SA 5005, AustraliaClinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaProstate 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.https://www.mdpi.com/2218-273X/15/1/23prostate cancer (PCa)tunnelling nanotubes (TNTs)extracellular vesicles (EVs)cellular bridgesandrogen receptor (AR)ezrin |
| spellingShingle | Jessica K. Heatlie Joanna Lazniewska Courtney R. Moore Ian R. D. Johnson Bukuru D. Nturubika Ruth Williams Mark P. Ward John J. O’Leary Lisa M. Butler Doug A. Brooks Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication Biomolecules prostate cancer (PCa) tunnelling nanotubes (TNTs) extracellular vesicles (EVs) cellular bridges androgen receptor (AR) ezrin |
| title | Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication |
| title_full | Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication |
| title_fullStr | Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication |
| title_full_unstemmed | Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication |
| title_short | Extracellular Vesicles and Tunnelling Nanotubes as Mediators of Prostate Cancer Intercellular Communication |
| title_sort | extracellular vesicles and tunnelling nanotubes as mediators of prostate cancer intercellular communication |
| topic | prostate cancer (PCa) tunnelling nanotubes (TNTs) extracellular vesicles (EVs) cellular bridges androgen receptor (AR) ezrin |
| url | https://www.mdpi.com/2218-273X/15/1/23 |
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