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
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Adiposity
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Adoptive Transfer
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Animals
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor
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Coculture Techniques
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Diet, Fat-Restricted
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Disease Models, Animal
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Disease Progression
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Female
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Gene Expression Regulation, Neoplastic
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Granulocyte-Macrophage Colony-Stimulating Factor / blood
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
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Interleukin-5 / blood
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Interleukin-5 / metabolism*
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Lung / metabolism*
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Lung / pathology
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism*
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Mice, SCID
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Mice, Transgenic
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Neutrophil Infiltration*
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Neutrophils / metabolism*
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Neutrophils / pathology
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Neutrophils / transplantation
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Obesity / complications
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Obesity / diet therapy
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Obesity / metabolism*
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Obesity / pathology
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Pneumonia / etiology
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Pneumonia / metabolism*
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Pneumonia / pathology
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Pneumonia / prevention & control
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Signal Transduction
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Time Factors
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Tumor Microenvironment
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Weight Loss
Substances
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IL5 protein, human
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Interleukin-5
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Granulocyte-Macrophage Colony-Stimulating Factor