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PXD027628

PXD027628 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRadiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
DescriptionRadiotherapy, a treatment modality received by more than half of all cancer patients, remains one of the most effective approaches to achieve local tumour control. Despite increased accuracy driven by technological advances, healthy tissue injury due to off-target radiation exposure can still occur. In this study, we sought to understand the biological effect of radiation-mediated injury to the lung in the context of cancer metastasis, since we had previously reported that tissue regeneration is a feature of the metastatic microenvironment of this organ. We have exposed healthy mouse lung tissue to radiation prior to the induction of metastasis and observed a strong enhancement of cancer cell growth. Lung tissue was preconditioned into a profoundly tumour-supportive microenvironment governed by enhanced regenerative Notch signalling. Most importantly, we found that locally activated neutrophils were key drivers of these tissue perturbations, significantly increasing the metastatic proficiency of irradiated lung tissue and endowing arriving cancer cells with an augmented stemness phenotype. We show that by preventing neutrophil-dependent Notch activation in the irradiated tissue, we were able to significantly offset the radiation-enhanced metastases. Mechanistically, we identified the release of neutrophil granules as the effectors of the pro-tumorigenic preconditioning of the irradiated lung tissue. These findings not only reveal a novel tumour-supportive function of neutrophils in the context of tissue-injury, but also have important clinical implications by suggesting targeting their activity could maximise the success of radiotherapy for the treatment of cancer.
HostingRepositoryPRIDE
AnnounceDate2021-12-13
AnnouncementXMLSubmission_2021-12-13_04:33:04.024.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMark Skehel
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; acetylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-28 06:07:04ID requested
12021-12-13 04:33:04announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Radiotherapy, Neutrophil granules, metastasis, cancer
Contact List
Ilaria Malanchi
contact affiliationTumour Host Interaction laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London
contact emailIlaria.Malanchi@crick.ac.uk
lab head
Mark Skehel
contact affiliationFrancis Crick Institute
contact emailskehelm@crick.ac.uk
dataset submitter
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Dataset FTP location
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