Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome
Extracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies and poor patient prognosis. Given the high relevance of the information provided by cancer cell secr...
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MDPI AG
2024-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/7/571 |
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| author | Fabrizio Di Giuseppe Lucia Ricci-Vitiani Roberto Pallini Roberta Di Pietro Patrizia Di Iorio Giuliano Ascani Renata Ciccarelli Stefania Angelucci |
| author_facet | Fabrizio Di Giuseppe Lucia Ricci-Vitiani Roberto Pallini Roberta Di Pietro Patrizia Di Iorio Giuliano Ascani Renata Ciccarelli Stefania Angelucci |
| author_sort | Fabrizio Di Giuseppe |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies and poor patient prognosis. Given the high relevance of the information provided by cancer cell secretome, we performed a proteomic analysis of microvesicles (MVs) and exosomes (EXOs) released from GBM-derived stem cells (GSCs). The latter, obtained from the brain of GBM patients, expressed P2X7 receptors (P2X7Rs), which positively correlate with GBM growth and invasiveness. P2X7R stimulation of GSCs caused significant changes in the EV content, mostly ex novo inducing or upregulating the expression of proteins related to cytoskeleton reorganization, cell motility/spreading, energy supply, protection against oxidative stress, chromatin remodeling, and transcriptional regulation. Most of the induced/upregulated proteins have already been identified as GBM diagnostic/prognostic factors, while others have only been reported in peripheral tumors. Our findings indicate that P2X7R stimulation enhances the transport and, therefore, possible intercellular exchange of GBM aggressiveness-increasing proteins by GSC-derived EVs. Thus, P2X7Rs could be considered a new druggable target of human GBM, although these data need to be confirmed in larger experimental sets. |
| first_indexed | 2024-04-24T10:47:33Z |
| format | Article |
| id | doaj.art-2e0be038e518432d9b9b20b5586049b9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T10:47:33Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-2e0be038e518432d9b9b20b5586049b92024-04-12T13:16:25ZengMDPI AGCells2073-44092024-03-0113757110.3390/cells13070571Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their SecretomeFabrizio Di Giuseppe0Lucia Ricci-Vitiani1Roberto Pallini2Roberta Di Pietro3Patrizia Di Iorio4Giuliano Ascani5Renata Ciccarelli6Stefania Angelucci7Department of Innovative Technologies in Medicine and Dentistry, ‘G. d’Annunzio’ University of Chieti-Pescara, Via Vestini 31, 66100 Chieti, ItalyDepartment of Medical, Oral and Biotechnological Sciences, ‘G d’Annunzio’ University of Chieti-Pescara, Via Vestini 31, 66100 Chieti, ItalyDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Via Regina Elena 299, 00161 Rome, ItalyInstitute of Neurosurgery, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, ItalyDepartment of Medicine and Aging Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, Via Vestini 31, 66100 Chieti, ItalyUOSD Maxillofacial Surgery, Azienda Sanitaria Locale di Pescara, Via Renato Paolini 47, 65124 Pescara, ItalyCenter for Advanced Studies and Technology (CAST), ‘G d’Annunzio’ University of Chieti-Pescara, Via L Polacchi 13, 66100 Chieti, ItalyDepartment of Innovative Technologies in Medicine and Dentistry, ‘G. d’Annunzio’ University of Chieti-Pescara, Via Vestini 31, 66100 Chieti, ItalyExtracellular vesicles (EVs) are secreted from many tumors, including glioblastoma multiforme (GBM), the most common and lethal brain tumor in adults, which shows high resistance to current therapies and poor patient prognosis. Given the high relevance of the information provided by cancer cell secretome, we performed a proteomic analysis of microvesicles (MVs) and exosomes (EXOs) released from GBM-derived stem cells (GSCs). The latter, obtained from the brain of GBM patients, expressed P2X7 receptors (P2X7Rs), which positively correlate with GBM growth and invasiveness. P2X7R stimulation of GSCs caused significant changes in the EV content, mostly ex novo inducing or upregulating the expression of proteins related to cytoskeleton reorganization, cell motility/spreading, energy supply, protection against oxidative stress, chromatin remodeling, and transcriptional regulation. Most of the induced/upregulated proteins have already been identified as GBM diagnostic/prognostic factors, while others have only been reported in peripheral tumors. Our findings indicate that P2X7R stimulation enhances the transport and, therefore, possible intercellular exchange of GBM aggressiveness-increasing proteins by GSC-derived EVs. Thus, P2X7Rs could be considered a new druggable target of human GBM, although these data need to be confirmed in larger experimental sets.https://www.mdpi.com/2073-4409/13/7/571glioblastoma-derived stem-like cells (GSCs)microvesiclesexosomesproteomic analysisP2X7 receptors |
| spellingShingle | Fabrizio Di Giuseppe Lucia Ricci-Vitiani Roberto Pallini Roberta Di Pietro Patrizia Di Iorio Giuliano Ascani Renata Ciccarelli Stefania Angelucci Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome Cells glioblastoma-derived stem-like cells (GSCs) microvesicles exosomes proteomic analysis P2X7 receptors |
| title | Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome |
| title_full | Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome |
| title_fullStr | Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome |
| title_full_unstemmed | Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome |
| title_short | Changes Induced by P2X7 Receptor Stimulation of Human Glioblastoma Stem Cells in the Proteome of Extracellular Vesicles Isolated from Their Secretome |
| title_sort | changes induced by p2x7 receptor stimulation of human glioblastoma stem cells in the proteome of extracellular vesicles isolated from their secretome |
| topic | glioblastoma-derived stem-like cells (GSCs) microvesicles exosomes proteomic analysis P2X7 receptors |
| url | https://www.mdpi.com/2073-4409/13/7/571 |
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