Cargando…

Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells

Radiation therapy is one of the most effective methods of tumor eradication; however, in some forms of neuroblastoma, radiation can increase the risk of secondary neoplasms, due to the ability of irradiated cells to transmit pro-survival signals to non-irradiated cells through vesicle secretion. The...

Descripción completa

Detalles Bibliográficos
Autores principales: Tortolici, Flavia, Vumbaca, Simone, Incocciati, Bernadette, Dayal, Renu, Aquilano, Katia, Giovanetti, Anna, Rufini, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827279/
https://www.ncbi.nlm.nih.gov/pubmed/33430027
http://dx.doi.org/10.3390/cells10010107
_version_ 1783640723869925376
author Tortolici, Flavia
Vumbaca, Simone
Incocciati, Bernadette
Dayal, Renu
Aquilano, Katia
Giovanetti, Anna
Rufini, Stefano
author_facet Tortolici, Flavia
Vumbaca, Simone
Incocciati, Bernadette
Dayal, Renu
Aquilano, Katia
Giovanetti, Anna
Rufini, Stefano
author_sort Tortolici, Flavia
collection PubMed
description Radiation therapy is one of the most effective methods of tumor eradication; however, in some forms of neuroblastoma, radiation can increase the risk of secondary neoplasms, due to the ability of irradiated cells to transmit pro-survival signals to non-irradiated cells through vesicle secretion. The aims of this study were to characterize the vesicles released by the human neuroblastoma cell line SH-SY5Y following X-ray radiations and their ability to increase invasiveness in non-irradiated SH-SY5Y cells. We first purified the extracellular vesicles released by the SH-SY5Y cells following X-rays, and then determined their total amount, dimensions, membrane protein composition, and cellular uptake. We also examined the effects of these extracellular vesicles on viability, migration, and DNA damage in recipient SH-SY5Y cells. We found that exposure to X-rays increased the release of extracellular vesicles and altered their protein composition. These vesicles were readily uptaken by non-irradiated cells, inducing an increase in viability, migration, and radio-resistance. The same results were obtained in an MYCN-amplified SK-N-BE cell line. Our study demonstrates that vesicles released from irradiated neuroblastoma cells stimulate proliferation and invasiveness that correlate with the epithelial to mesenchymal transition in non-irradiated cells. Moreover, our results suggest that, at least in neuroblastomas, targeting the extracellular vesicles may represent a novel therapeutic approach to counteract the side effects associated with radiotherapy.
format Online
Article
Text
id pubmed-7827279
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78272792021-01-25 Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells Tortolici, Flavia Vumbaca, Simone Incocciati, Bernadette Dayal, Renu Aquilano, Katia Giovanetti, Anna Rufini, Stefano Cells Article Radiation therapy is one of the most effective methods of tumor eradication; however, in some forms of neuroblastoma, radiation can increase the risk of secondary neoplasms, due to the ability of irradiated cells to transmit pro-survival signals to non-irradiated cells through vesicle secretion. The aims of this study were to characterize the vesicles released by the human neuroblastoma cell line SH-SY5Y following X-ray radiations and their ability to increase invasiveness in non-irradiated SH-SY5Y cells. We first purified the extracellular vesicles released by the SH-SY5Y cells following X-rays, and then determined their total amount, dimensions, membrane protein composition, and cellular uptake. We also examined the effects of these extracellular vesicles on viability, migration, and DNA damage in recipient SH-SY5Y cells. We found that exposure to X-rays increased the release of extracellular vesicles and altered their protein composition. These vesicles were readily uptaken by non-irradiated cells, inducing an increase in viability, migration, and radio-resistance. The same results were obtained in an MYCN-amplified SK-N-BE cell line. Our study demonstrates that vesicles released from irradiated neuroblastoma cells stimulate proliferation and invasiveness that correlate with the epithelial to mesenchymal transition in non-irradiated cells. Moreover, our results suggest that, at least in neuroblastomas, targeting the extracellular vesicles may represent a novel therapeutic approach to counteract the side effects associated with radiotherapy. MDPI 2021-01-08 /pmc/articles/PMC7827279/ /pubmed/33430027 http://dx.doi.org/10.3390/cells10010107 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tortolici, Flavia
Vumbaca, Simone
Incocciati, Bernadette
Dayal, Renu
Aquilano, Katia
Giovanetti, Anna
Rufini, Stefano
Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title_full Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title_fullStr Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title_full_unstemmed Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title_short Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
title_sort ionizing radiation-induced extracellular vesicle release promotes akt-associated survival response in sh-sy5y neuroblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827279/
https://www.ncbi.nlm.nih.gov/pubmed/33430027
http://dx.doi.org/10.3390/cells10010107
work_keys_str_mv AT tortoliciflavia ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT vumbacasimone ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT incocciatibernadette ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT dayalrenu ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT aquilanokatia ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT giovanettianna ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells
AT rufinistefano ionizingradiationinducedextracellularvesiclereleasepromotesaktassociatedsurvivalresponseinshsy5yneuroblastomacells