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

Autor: Nolan E; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Bridgeman VL; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Ombrato L; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK.; Barts Cancer Institute, Queen Mary University of London, London, UK., Karoutas A; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Rabas N; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Sewnath CAN; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Vasquez M; Cancer Immunology Unit, UCL Cancer Institute, University College London, London, UK., Rodrigues FS; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK., Horswell S; Bioinformatics & Biostatistics Unit, The Francis Crick Institute, London, UK., Faull P; Proteomics Unit, The Francis Crick Institute, London, UK.; Center for Biomedical Research Support Biological Mass Spectrometry Facility, The University of Texas at Austin, Austin, TX, USA., Carter R; Preclinical Radiotherapy TTP, CRUK-City of London Centre, UCL Cancer Institute, University College London, London, UK., Malanchi I; Tumour Host Interaction laboratory, The Francis Crick Institute, London, UK. Ilaria.Malanchi@crick.ac.uk.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2022 Feb; Vol. 3 (2), pp. 173-187. Date of Electronic Publication: 2022 Feb 24.
DOI: 10.1038/s43018-022-00336-7
Abstrakt: Radiotherapy is one of the most effective approaches to achieve tumor 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 before the induction of metastasis and observed a strong enhancement of cancer cell growth. We found that locally activated neutrophils were key drivers of the tumor-supportive preconditioning of the lung microenvironment, governed by enhanced regenerative Notch signaling. 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. Crown.)
Databáze: MEDLINE
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