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Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF.

作者信息

Quail Daniela F, Olson Oakley C, Bhardwaj Priya, Walsh Logan A, Akkari Leila, Quick Marsha L, Chen I-Chun, Wendel Nils, Ben-Chetrit Nir, Walker Jeanne, Holt Peter R, Dannenberg Andrew J, Joyce Johanna A

机构信息

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA.

出版信息

Nat Cell Biol. 2017 Aug;19(8):974-987. doi: 10.1038/ncb3578. Epub 2017 Jul 24.


DOI:10.1038/ncb3578
PMID:28737771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6759922/
Abstract

Obesity is associated with chronic, low-grade inflammation, which can disrupt homeostasis within tissue microenvironments. Given the correlation between obesity and relative risk of death from cancer, we investigated whether obesity-associated inflammation promotes metastatic progression. We demonstrate that obesity causes lung neutrophilia in otherwise normal mice, which is further exacerbated by the presence of a primary tumour. The increase in lung neutrophils translates to increased breast cancer metastasis to this site, in a GM-CSF- and IL5-dependent manner. Importantly, weight loss is sufficient to reverse this effect, and reduce serum levels of GM-CSF and IL5 in both mouse models and humans. Our data indicate that special consideration of the obese patient population is critical for effective management of cancer progression.

摘要

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本文引用的文献

[1]
Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

J Endocr Soc. 2017-4-25

[2]
Pre-metastatic niches: organ-specific homes for metastases.

Nat Rev Cancer. 2017-3-17

[3]
Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Nature. 2017-1-5

[4]
Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils.

Cancer Cell. 2016-8-8

[5]
Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

Cancer Cell. 2016-7-11

[6]
Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells.

Cancer Discov. 2016-6

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Clin Cancer Res. 2016-5-1

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Immunotherapy. 2016

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Neutrophils support lung colonization of metastasis-initiating breast cancer cells.

Nature. 2015-12-17

[10]
Obesity Correlation With Metastases Development and Response to First-Line Metastatic Chemotherapy in Breast Cancer.

Clin Med Insights Oncol. 2015-11-24

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