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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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Detalles Bibliográficos
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
Descripción
Sumario: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.