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