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Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells
Radiation is a highly efficient therapy in squamous head and neck carcinoma (HNSCC) treatment. However, local recurrence and metastasis are common complications. Recent evidence shows that cancer-cell-derived exosomes modify tumour cell movement and metastasis. In this study, we link radiation-induc...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622080/ https://www.ncbi.nlm.nih.gov/pubmed/28963552 http://dx.doi.org/10.1038/s41598-017-12403-6 |
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author | Mutschelknaus, Lisa Azimzadeh, Omid Heider, Theresa Winkler, Klaudia Vetter, Marcus Kell, Rosemarie Tapio, Soile Merl-Pham, Juliane Huber, Stephan M. Edalat, Lena Radulović, Vanja Anastasov, Nataša Atkinson, Michael J. Moertl, Simone |
author_facet | Mutschelknaus, Lisa Azimzadeh, Omid Heider, Theresa Winkler, Klaudia Vetter, Marcus Kell, Rosemarie Tapio, Soile Merl-Pham, Juliane Huber, Stephan M. Edalat, Lena Radulović, Vanja Anastasov, Nataša Atkinson, Michael J. Moertl, Simone |
author_sort | Mutschelknaus, Lisa |
collection | PubMed |
description | Radiation is a highly efficient therapy in squamous head and neck carcinoma (HNSCC) treatment. However, local recurrence and metastasis are common complications. Recent evidence shows that cancer-cell-derived exosomes modify tumour cell movement and metastasis. In this study, we link radiation-induced changes of exosomes to their ability to promote migration of recipient HNSCC cells. We demonstrate that exosomes isolated from irradiated donor cells boost the motility of the HNSCC cells BHY and FaDu. Molecular data identified enhanced AKT-signalling, manifested through increased phospho-mTOR, phospho-rpS6 and MMP2/9 protease activity, as underlying mechanism. AKT-inhibition blocked the pro-migratory action, suggesting AKT-signalling as key player in exosome-mediated migration. Proteomic analysis of exosomes isolated from irradiated and non-irradiated BHY donor cells identified 39 up- and 36 downregulated proteins. In line with the observed pro-migratory effect of exosomes isolated from irradiated cells protein function analysis assigned the deregulated exosomal proteins to cell motility and AKT-signalling. Together, our findings demonstrate that exosomes derived from irradiated HNSCC cells confer a migratory phenotype to recipient cancer cells. This is possibly due to radiation-regulated exosomal proteins that increase AKT-signalling. We conclude that exosomes may act as driver of HNSCC progression during radiotherapy and are therefore attractive targets to improve radiation therapy strategies. |
format | Online Article Text |
id | pubmed-5622080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56220802017-10-12 Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells Mutschelknaus, Lisa Azimzadeh, Omid Heider, Theresa Winkler, Klaudia Vetter, Marcus Kell, Rosemarie Tapio, Soile Merl-Pham, Juliane Huber, Stephan M. Edalat, Lena Radulović, Vanja Anastasov, Nataša Atkinson, Michael J. Moertl, Simone Sci Rep Article Radiation is a highly efficient therapy in squamous head and neck carcinoma (HNSCC) treatment. However, local recurrence and metastasis are common complications. Recent evidence shows that cancer-cell-derived exosomes modify tumour cell movement and metastasis. In this study, we link radiation-induced changes of exosomes to their ability to promote migration of recipient HNSCC cells. We demonstrate that exosomes isolated from irradiated donor cells boost the motility of the HNSCC cells BHY and FaDu. Molecular data identified enhanced AKT-signalling, manifested through increased phospho-mTOR, phospho-rpS6 and MMP2/9 protease activity, as underlying mechanism. AKT-inhibition blocked the pro-migratory action, suggesting AKT-signalling as key player in exosome-mediated migration. Proteomic analysis of exosomes isolated from irradiated and non-irradiated BHY donor cells identified 39 up- and 36 downregulated proteins. In line with the observed pro-migratory effect of exosomes isolated from irradiated cells protein function analysis assigned the deregulated exosomal proteins to cell motility and AKT-signalling. Together, our findings demonstrate that exosomes derived from irradiated HNSCC cells confer a migratory phenotype to recipient cancer cells. This is possibly due to radiation-regulated exosomal proteins that increase AKT-signalling. We conclude that exosomes may act as driver of HNSCC progression during radiotherapy and are therefore attractive targets to improve radiation therapy strategies. Nature Publishing Group UK 2017-09-29 /pmc/articles/PMC5622080/ /pubmed/28963552 http://dx.doi.org/10.1038/s41598-017-12403-6 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mutschelknaus, Lisa Azimzadeh, Omid Heider, Theresa Winkler, Klaudia Vetter, Marcus Kell, Rosemarie Tapio, Soile Merl-Pham, Juliane Huber, Stephan M. Edalat, Lena Radulović, Vanja Anastasov, Nataša Atkinson, Michael J. Moertl, Simone Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title | Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title_full | Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title_fullStr | Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title_full_unstemmed | Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title_short | Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
title_sort | radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622080/ https://www.ncbi.nlm.nih.gov/pubmed/28963552 http://dx.doi.org/10.1038/s41598-017-12403-6 |
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