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

doi:10.1038/ncb3578

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

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

Authors

Daniela F Quail¹, Oakley C Olson¹, Priya Bhardwaj², Logan A Walsh³, Leila Akkari^{1

4

5}, Marsha L Quick¹, I-Chun Chen², Nils Wendel², Nir Ben-Chetrit^{1

2}, Jeanne Walker⁶, Peter R Holt⁶, Andrew J Dannenberg², Johanna A Joyce^{1

4

5}

Affiliations

¹ Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
² Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
³ Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
⁴ Ludwig Institute for Cancer Research, Lausanne 1066, Switzerland.
⁵ Department of Oncology, University of Lausanne, Lausanne 1066, Switzerland.
⁶ Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10065, USA.

PMID: 28737771
PMCID: PMC6759922
DOI: 10.1038/ncb3578

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.

MeSH terms

Adiposity
Adoptive Transfer
Animals
Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Coculture Techniques
Diet, Fat-Restricted
Disease Models, Animal
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Granulocyte-Macrophage Colony-Stimulating Factor / blood
Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
Interleukin-5 / blood
Interleukin-5 / metabolism*
Lung / metabolism*
Lung / pathology
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / prevention & control
Lung Neoplasms / secondary
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Neutrophil Infiltration*
Neutrophils / metabolism*
Neutrophils / pathology
Neutrophils / transplantation
Obesity / complications
Obesity / diet therapy
Obesity / metabolism*
Obesity / pathology
Pneumonia / etiology
Pneumonia / metabolism*
Pneumonia / pathology
Pneumonia / prevention & control
Signal Transduction
Time Factors
Tumor Microenvironment
Weight Loss

Substances

IL5 protein, human
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor

Abstract

MeSH terms

Substances

Grants and funding