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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...

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Autores principales: Pinto, Giulia, Saenz-de-Santa-Maria, Inés, Chastagner, Patricia, Perthame, Emeline, Delmas, Caroline, Toulas, Christine, Moyal-Jonathan-Cohen, Elizabeth, Brou, Christel, Zurzolo, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
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.
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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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