Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer.
Adipose Tissue
/ pathology
Animals
Carcinogenesis
/ metabolism
Cell Line, Tumor
Cytokine Receptor gp130
/ metabolism
Diet
Female
Humans
Interleukin-6
/ metabolism
Macrophages
/ metabolism
Mammary Glands, Animal
/ pathology
Mammary Glands, Human
/ pathology
Mice, Inbred C57BL
Neoplastic Stem Cells
/ pathology
Obesity
/ pathology
Phenotype
Triple Negative Breast Neoplasms
/ pathology
Weight Loss
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
03 06 2019
03 06 2019
Historique:
received:
22
08
2018
revised:
27
01
2019
accepted:
29
03
2019
pubmed:
6
5
2019
medline:
15
4
2020
entrez:
5
5
2019
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 31053611
pii: jem.20181616
doi: 10.1084/jem.20181616
pmc: PMC6547867
doi:
Substances chimiques
Il6st protein, mouse
0
Interleukin-6
0
Cytokine Receptor gp130
133483-10-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1345-1358Subventions
Organisme : NCI NIH HHS
ID : R01 CA184494
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK102960
Pays : United States
Organisme : NCI NIH HHS
ID : F99 CA212477
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107868
Pays : United States
Organisme : British Heart Foundation
ID : RG/13/11/30384
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Informations de copyright
© 2019 Tiwari et al.
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