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

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

Research output: Contribution to journalArticle

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)974-987
Number of pages14
JournalNature Cell Biology
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Cell Biology

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