AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles
Abstract Background Extracellular vesicles (EVs) are membrane-enclosed particles released systemically by all cells, including tumours. Tumour EVs have been shown to manipulate their local environments as well as distal targets to sustain the tumour in a variety of tumours, including glioblastoma (G...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-022-00888-2 |
| _version_ | 1811273769892708352 |
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| author | Laura Simone Francesco Pisani Elena Binda Antonio Frigeri Angelo L. Vescovi Maria Svelto Grazia P. Nicchia |
| author_facet | Laura Simone Francesco Pisani Elena Binda Antonio Frigeri Angelo L. Vescovi Maria Svelto Grazia P. Nicchia |
| author_sort | Laura Simone |
| collection | DOAJ |
| description | Abstract Background Extracellular vesicles (EVs) are membrane-enclosed particles released systemically by all cells, including tumours. Tumour EVs have been shown to manipulate their local environments as well as distal targets to sustain the tumour in a variety of tumours, including glioblastoma (GBM). We have previously demonstrated the dual role of the glial water channel aquaporin-4 (AQP4) protein in glioma progression or suppression depending on its aggregation state. However, its possible role in communication mechanisms in the microenvironment of malignant gliomas remains to be unveiled. Results Here we show that in GBM cells AQP4 is released via EVs that are able to affect the GBM microenvironment. To explore this role, EVs derived from invasive GBM cells expressing AQP4-tetramers or apoptotic GBM cells expressing orthogonal arrays of particles (AQP4-OAPs) were isolated, using a differential ultracentrifugation method, and were added to pre-seeded GBM cells. Confocal microscopy analysis was used to visualize the interaction and uptake of AQP4-containing EVs by recipient cells. Chemoinvasion and Caspase3/7 activation assay, performed on recipient cells after EVs uptake, revealed that EVs produced by AQP4-tetramers expressing cells were able to drive surrounding tumour cells toward the migratory phenotype, whereas EVs produced by AQP4-OAPs expressing cells drive them toward the apoptosis pathway. Conclusion This study demonstrates that the different GBM cell phenotypes can be transferred by AQP4-containing EVs able to influence tumour cell fate toward invasiveness or apoptosis. This study opens a new perspective on the role of AQP4 in the brain tumour microenvironment associated with the EV-dependent communication mechanism. Graphical Abstract |
| first_indexed | 2024-04-12T23:05:28Z |
| format | Article |
| id | doaj.art-116bc5d577ce4525ba2e1cafa9dd446b |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-12T23:05:28Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-116bc5d577ce4525ba2e1cafa9dd446b2022-12-22T03:12:55ZengBMCCell & Bioscience2045-37012022-09-0112111710.1186/s13578-022-00888-2AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesiclesLaura Simone0Francesco Pisani1Elena Binda2Antonio Frigeri3Angelo L. Vescovi4Maria Svelto5Grazia P. Nicchia6Cancer Stem Cells Unit, Fondazione IRCCS Casa Sollievo della SofferenzaDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroCancer Stem Cells Unit, Fondazione IRCCS Casa Sollievo della SofferenzaSchool of Medicine, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Aldo MoroCancer Stem Cells Unit, Fondazione IRCCS Casa Sollievo della SofferenzaDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroAbstract Background Extracellular vesicles (EVs) are membrane-enclosed particles released systemically by all cells, including tumours. Tumour EVs have been shown to manipulate their local environments as well as distal targets to sustain the tumour in a variety of tumours, including glioblastoma (GBM). We have previously demonstrated the dual role of the glial water channel aquaporin-4 (AQP4) protein in glioma progression or suppression depending on its aggregation state. However, its possible role in communication mechanisms in the microenvironment of malignant gliomas remains to be unveiled. Results Here we show that in GBM cells AQP4 is released via EVs that are able to affect the GBM microenvironment. To explore this role, EVs derived from invasive GBM cells expressing AQP4-tetramers or apoptotic GBM cells expressing orthogonal arrays of particles (AQP4-OAPs) were isolated, using a differential ultracentrifugation method, and were added to pre-seeded GBM cells. Confocal microscopy analysis was used to visualize the interaction and uptake of AQP4-containing EVs by recipient cells. Chemoinvasion and Caspase3/7 activation assay, performed on recipient cells after EVs uptake, revealed that EVs produced by AQP4-tetramers expressing cells were able to drive surrounding tumour cells toward the migratory phenotype, whereas EVs produced by AQP4-OAPs expressing cells drive them toward the apoptosis pathway. Conclusion This study demonstrates that the different GBM cell phenotypes can be transferred by AQP4-containing EVs able to influence tumour cell fate toward invasiveness or apoptosis. This study opens a new perspective on the role of AQP4 in the brain tumour microenvironment associated with the EV-dependent communication mechanism. Graphical Abstracthttps://doi.org/10.1186/s13578-022-00888-2GBMEVsTumour environmentApoptosisMigrationAQP4 |
| spellingShingle | Laura Simone Francesco Pisani Elena Binda Antonio Frigeri Angelo L. Vescovi Maria Svelto Grazia P. Nicchia AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles Cell & Bioscience GBM EVs Tumour environment Apoptosis Migration AQP4 |
| title | AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| title_full | AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| title_fullStr | AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| title_full_unstemmed | AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| title_short | AQP4-dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| title_sort | aqp4 dependent glioma cell features affect the phenotype of surrounding cells via extracellular vesicles |
| topic | GBM EVs Tumour environment Apoptosis Migration AQP4 |
| url | https://doi.org/10.1186/s13578-022-00888-2 |
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