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Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization

Radiotherapy is one of the most effective approaches to achieve tumour control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. In this study, we used a model of acute radiation injury to the lung in the context of cancer metastasis, to understand th...

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Autores principales: Nolan, Emma, Bridgeman, Victoria Louise, Ombrato, Luigi, Karoutas, Adam, Rabas, Nicolas, Sewnath, Celine Angeli Natascha, Vasquez, Marcos, Rodrigues, Felipe Silva, Horswell, Stuart, Faull, Peter, Carter, Rebecca, Malanchi, Ilaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612918/
https://www.ncbi.nlm.nih.gov/pubmed/35221334
http://dx.doi.org/10.1038/s43018-022-00336-7
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author Nolan, Emma
Bridgeman, Victoria Louise
Ombrato, Luigi
Karoutas, Adam
Rabas, Nicolas
Sewnath, Celine Angeli Natascha
Vasquez, Marcos
Rodrigues, Felipe Silva
Horswell, Stuart
Faull, Peter
Carter, Rebecca
Malanchi, Ilaria
author_facet Nolan, Emma
Bridgeman, Victoria Louise
Ombrato, Luigi
Karoutas, Adam
Rabas, Nicolas
Sewnath, Celine Angeli Natascha
Vasquez, Marcos
Rodrigues, Felipe Silva
Horswell, Stuart
Faull, Peter
Carter, Rebecca
Malanchi, Ilaria
author_sort Nolan, Emma
collection PubMed
description Radiotherapy is one of the most effective approaches to achieve tumour control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. In this study, we used a model of acute radiation injury to the lung in the context of cancer metastasis, to understand the biological link between tissue damage and cancer progression. We exposed healthy mouse lung tissue to radiation prior to the induction of metastasis and observed a strong enhancement of cancer cell growth. We found that locally activated neutrophils were key drivers of the tumour-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signalling. Importantly, these tissue perturbations endowed arriving cancer cells with an augmented stemness phenotype. By preventing neutrophil-dependent Notch activation, via blocking degranulation, we were able to significantly offset the radiation-enhanced metastases. This work highlights a pro-tumorigenic activity of neutrophils, which is likely linked to their tissue regenerative functions.
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spelling pubmed-76129182022-08-24 Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization Nolan, Emma Bridgeman, Victoria Louise Ombrato, Luigi Karoutas, Adam Rabas, Nicolas Sewnath, Celine Angeli Natascha Vasquez, Marcos Rodrigues, Felipe Silva Horswell, Stuart Faull, Peter Carter, Rebecca Malanchi, Ilaria Nat Cancer Article Radiotherapy is one of the most effective approaches to achieve tumour control in cancer patients, although healthy tissue injury due to off-target radiation exposure can occur. In this study, we used a model of acute radiation injury to the lung in the context of cancer metastasis, to understand the biological link between tissue damage and cancer progression. We exposed healthy mouse lung tissue to radiation prior to the induction of metastasis and observed a strong enhancement of cancer cell growth. We found that locally activated neutrophils were key drivers of the tumour-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signalling. Importantly, these tissue perturbations endowed arriving cancer cells with an augmented stemness phenotype. By preventing neutrophil-dependent Notch activation, via blocking degranulation, we were able to significantly offset the radiation-enhanced metastases. This work highlights a pro-tumorigenic activity of neutrophils, which is likely linked to their tissue regenerative functions. 2022-02-01 2022-02-24 /pmc/articles/PMC7612918/ /pubmed/35221334 http://dx.doi.org/10.1038/s43018-022-00336-7 Text en https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Nolan, Emma
Bridgeman, Victoria Louise
Ombrato, Luigi
Karoutas, Adam
Rabas, Nicolas
Sewnath, Celine Angeli Natascha
Vasquez, Marcos
Rodrigues, Felipe Silva
Horswell, Stuart
Faull, Peter
Carter, Rebecca
Malanchi, Ilaria
Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title_full Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title_fullStr Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title_full_unstemmed Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title_short Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
title_sort radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612918/
https://www.ncbi.nlm.nih.gov/pubmed/35221334
http://dx.doi.org/10.1038/s43018-022-00336-7
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