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

肥胖通过 IL5 和 GM-CSF 改变肺癌髓系细胞格局,从而增强乳腺癌转移

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作者: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

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.

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