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

DF Quail, OC Olson, P Bhardwaj, LA Walsh… - Nature cell …, 2017 - nature.com
DF Quail, OC Olson, P Bhardwaj, LA Walsh, L Akkari, ML Quick, IC Chen, N Wendel
Nature cell biology, 2017nature.com
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 …
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.
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