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Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer.
Citation | “Metabolically Activated Adipose Tissue Macrophages Link Obesity To Triple-Negative Breast Cancer.”. The Journal Of Experimental Medicine, pp. 1345-1358. . |
Center | University of Chicago |
Author | Payal Tiwari, Ariane Blank, Chang Cui, Kelly Q Schoenfelt, Guolin Zhou, Yanfei Xu, Galina Khramtsova, Funmi Olopade, Ajay M Shah, Seema A Khan, Marsha Rich Rosner, Lev Becker |
Abstract |
Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Here, we show that obesity reprograms mammary adipose tissue macrophages to a pro-inflammatory metabolically activated phenotype (MMe) that alters the niche to support tumor formation. Unlike pro-inflammatory M1 macrophages that antagonize tumorigenesis, MMe macrophages are pro-tumorigenic and represent the dominant macrophage phenotype in mammary adipose tissue of obese humans and mice. MMe macrophages release IL-6 in an NADPH oxidase 2 (NOX2)-dependent manner, which signals through glycoprotein 130 (GP130) on TNBC cells to promote stem-like properties including tumor formation. Deleting in myeloid cells or depleting GP130 in TNBC cells attenuates obesity-augmented TNBC stemness. Moreover, weight loss reverses the effects of obesity on MMe macrophage inflammation and TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue as a mechanism for promoting TNBC stemness and tumorigenesis during obesity. |
Year of Publication |
2019
|
Journal |
The Journal of experimental medicine
|
Volume |
216
|
Issue |
6
|
Number of Pages |
1345-1358
|
Date Published |
12/2019
|
ISSN Number |
1540-9538
|
DOI |
10.1084/jem.20181616
|
Alternate Journal |
J. Exp. Med.
|
PMID |
31053611
|
PMCID |
PMC6547867
|
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