PXD027628-1

PXD027628 is an original dataset announced via ProteomeXchange.

Title	Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization
Description	Radiotherapy, 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.
HostingRepository	PRIDE
AnnounceDate	2021-12-13
AnnouncementXML	Submission_2021-12-13_04:33:04.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-28 06:07:04	ID requested
⏵ 1	2021-12-13 04:33:04	announced

Dataset with its publication pending

submitter keyword: Radiotherapy, Neutrophil granules, metastasis, cancer

Ilaria Malanchi
contact affiliation	Tumour Host Interaction laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London
contact email	Ilaria.Malanchi@crick.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/12/PXD027628

PRIDE project URI

• PRIDE
  1. PXD027628
     1. Label: PRIDE project
     2. Name: Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization