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