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


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.

SUBMITTER: Quail DF 

PROVIDER: S-EPMC6759922 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Quail Daniela F DF   Olson Oakley C OC   Bhardwaj Priya P   Walsh Logan A LA   Akkari Leila L   Quick Marsha L ML   Chen I-Chun IC   Wendel Nils N   Ben-Chetrit Nir N   Walker Jeanne J   Holt Peter R PR   Dannenberg Andrew J AJ   Joyce Johanna A JA  

Nature cell biology 20170724 8


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 c  ...[more]

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