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

ABSTRACT: We used our novel Cherry-niche system to specifically isolate cells from the metastatic niche of 4T1 lung metastasis and compared their profile with the one obtained isolating lungs cells distal from the tumour growth

ORGANISM(S): Mus musculus

PROVIDER: GSE181306 | GEO | 2021/12/01

REPOSITORIES: GEO

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Non-immune niche analysis in breast tumour derived lung metastasis

Project description:We used our novel Cherry-niche system to specifically isolate cells from the metastatic niche of 4T1 lung metastasis and compared their profile with the one obtained isolating lungs cells distal from the tumour growth.

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

Project description: Not available

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

Project 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.

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

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

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