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Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids
Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membra...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800365/ https://www.ncbi.nlm.nih.gov/pubmed/33245115 http://dx.doi.org/10.1042/BCJ20200710 |
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author | Pinto, Giulia Saenz-de-Santa-Maria, Inés Chastagner, Patricia Perthame, Emeline Delmas, Caroline Toulas, Christine Moyal-Jonathan-Cohen, Elizabeth Brou, Christel Zurzolo, Chiara |
author_facet | Pinto, Giulia Saenz-de-Santa-Maria, Inés Chastagner, Patricia Perthame, Emeline Delmas, Caroline Toulas, Christine Moyal-Jonathan-Cohen, Elizabeth Brou, Christel Zurzolo, Chiara |
author_sort | Pinto, Giulia |
collection | PubMed |
description | Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor's features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking. |
format | Online Article Text |
id | pubmed-7800365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78003652021-01-21 Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids Pinto, Giulia Saenz-de-Santa-Maria, Inés Chastagner, Patricia Perthame, Emeline Delmas, Caroline Toulas, Christine Moyal-Jonathan-Cohen, Elizabeth Brou, Christel Zurzolo, Chiara Biochem J Cancer Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor's features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking. Portland Press Ltd. 2021-01-15 2021-01-08 /pmc/articles/PMC7800365/ /pubmed/33245115 http://dx.doi.org/10.1042/BCJ20200710 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Cancer Pinto, Giulia Saenz-de-Santa-Maria, Inés Chastagner, Patricia Perthame, Emeline Delmas, Caroline Toulas, Christine Moyal-Jonathan-Cohen, Elizabeth Brou, Christel Zurzolo, Chiara Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title | Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title_full | Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title_fullStr | Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title_full_unstemmed | Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title_short | Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
title_sort | patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids |
topic | Cancer |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800365/ https://www.ncbi.nlm.nih.gov/pubmed/33245115 http://dx.doi.org/10.1042/BCJ20200710 |
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