Obesity-Associated Extracellular Matrix Remodeling Promotes a Macrophage Phenotype Similar to Tumor-Associated Macrophages.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
19
07
2018
revised:
03
06
2019
accepted:
18
06
2019
pubmed:
20
7
2019
medline:
28
3
2020
entrez:
20
7
2019
Statut:
ppublish
Résumé
Obesity is associated with adipose inflammation, defined by macrophages encircling dead adipocytes, as well as extracellular matrix (ECM) remodeling and increased risk of breast cancer. Whether ECM affects macrophage phenotype in obesity is uncertain. A better understanding of this relationship could be strategically important to reduce cancer risk or improve outcomes in the obese. Using clinical samples, computational approaches, and in vitro decellularized ECM models, this study quantified the relative abundance of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in human breast adipose tissue, determined molecular similarities between obesity and tumor-associated macrophages, and assessed the regulatory effect of obese versus lean ECM on macrophage phenotype. Our results suggest that breast adipose tissue contains more M2- than M1-biased macrophages across all body mass index categories. Obesity further increased M2-biased macrophages but did not affect M1-biased macrophage density. Gene Set Enrichment Analysis suggested that breast tissue macrophages from obese versus lean women are more similar to tumor-associated macrophages. These changes positively correlated with adipose tissue interstitial fibrosis, and in vitro experiments indicated that obese ECM directly stimulates M2-biased macrophage functions. However, mammographic density cannot be used as a clinical indicator of these changes. Collectively, these data suggest that obesity-associated interstitial fibrosis promotes a macrophage phenotype similar to tumor-associated macrophages, which may contribute to the link between obesity and breast cancer.
Identifiants
pubmed: 31323189
pii: S0002-9440(18)30607-2
doi: 10.1016/j.ajpath.2019.06.005
pmc: PMC6880774
pii:
doi:
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
2019-2035Subventions
Organisme : NCI NIH HHS
ID : R01 CA108539
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA210184
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIH HHS
ID : T32 OD011000
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215797
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA210180
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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