Obesity enhances lung metastasis through IL-5 and GM-CSF
Obese mice (diet-induced or genetic) show elevated neutrophil infiltration in lung. - Neutrophils also have different gene expression profile compared to lean mice: more activated, upreg homing/mobility genes. - Neutrophilia in lung also seen in primary tumour-bearing mice, but enhanced by obesity.
Increased breast cancer lung metastasis in obese mice, whether from primary tumour or by tail vein injection (increase evident by 48hr post injection).
Both neutrophilia and increased metastasis reversible by weight loss; do not occur in obesity-resistant Balb/c mice.
Among serum cytokines elevated in both obese mice and humans, GM-CSF and IL-5 can both individually recapitulate effects of obesity on neutrophilia and metastasis. - IL-5 treatment also increases GM-CSF, effects can be reversed by anti-GM-CSF. * IL-5 is negative regulator in adipose tissue - controls tissue expansion/insulin resistance; BUT is inflammatory to lung, implicated and targeted in asthma (IL-5R is expressed by 100% eosinophils).
Reduction in lung neutrophil infiltration and serum IL-5/GM-CSF observed in human patients after 10% weight loss.
Model: something in adipose tissue produces IL-5 --> induces IL-5R+ myeloid cells (but also IL-5R- CD3+ T cells?) to produce GM-CSF in lung --> recruits and expands neutrophils that prepare the metastatic niche.
Fig 8.
QUESTIONS: Authors show T cells are indispensable for IL-5 response, but do not explain how T cells mediate the response, without IL-5R expression? Which specific T cells are elevated? What do neutrophils do to prime the metastatic niche (probably covered in other publications)? The dual role of IL-5 in adipose tissue and in lung is interesting - how do these roles connect to each other?
Source: Quail, Daniela (Joyce, Johanna) 2017, Nature Cell Biology. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF http://www.nature.com/ncb/journal/v19/n8/full/ncb3578.html?foxtrotcallback=true
