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

• Published in: Nature cell biology Vol. 19; no. 8; pp. 974 - 987
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2017; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/31; 13/51; 14/1; 14/5; 14/63; 38/77; 59/5; 631/443/319/1642/393; 631/67; 631/67/322; 631/67/327; 64/60; 82; 82/79; Adiposity; Adoptive Transfer; Animal models; Animals; Body weight loss; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer Research; Cell Biology; Cell Line, Tumor; Coculture Techniques; Complications and side effects; Development and progression; Developmental Biology; Diet, Fat-Restricted; Disease Models, Animal; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Granulocyte colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - blood; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Health aspects; Homeostasis; Interleukin 5; Interleukin-5 - blood; Interleukin-5 - metabolism; Leukocytes (neutrophilic); Life Sciences; Lung - metabolism; Lung - pathology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Lungs; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Microenvironments; Neutrophil Infiltration; Neutrophilia; Neutrophils - metabolism; Neutrophils - pathology; Neutrophils - transplantation; Obesity; Obesity - complications; Obesity - diet therapy; Obesity - metabolism; Obesity - pathology; Physiological aspects; Pneumonia - etiology; Pneumonia - metabolism; Pneumonia - pathology; Pneumonia - prevention & control; Serum levels; Signal Transduction; Stem Cells; Time Factors; Tumor Microenvironment; Tumors; Weight control; Weight Loss; Weight reduction; United States
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb3578

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. Joyce and colleagues report that obesity promotes lung neutrophilia in mice, which in the presence of a primary breast tumour fosters metastasis to the lung in a manner dependent on GM-CSF and IL5.