ArticleThe American journal of pathology2019
Obesity-Associated Extracellular Matrix Remodeling Promotes a Macrophage Phenotype Similar to Tumor-Associated Macrophages.
Article in The American journal of pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 93 citations in OpenAlex.
- A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density.Breast cancer research and treatment · 2021Trial
- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- Association of stromal tumor infiltrating lymphocytes and body mass index with prognosis in esophageal squamous cell carcinoma patients.BMC cancer · 2026Article
- Obesity, Bariatric Surgery, and Cancer Risk: Nutritional Perspectives and Long-Term Clinical Implications.Nutrients · 2026Review
- Polarization increases nuclear stiffness in macrophages despite reduction in lamin A/C levels.npj biological physics and mechanics · 2026Article
- Macrophages in obesity-related breast cancer: mechanistic insights and therapeutic opportunities.Breast cancer research : BCR · 2025Review
- Advancing Breast Cancer Management Through an Enhanced Understanding of Disease Heterogeneity from Initiation to Metastasis.The American journal of pathology · 2025Article
- Review
- Nanofibrillar Cellulose Hydrogels with Anionic Surface Modifications for Modulating Macrophage Phenotype in 3D Culture.ACS applied materials & interfaces · 2025Article
- Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.NPJ breast cancer · 2025Article
- Lack of fibro-inflammatory response in human mammary adipose tissue in obesity.International journal of obesity (2005) · 2025Article
- Focusing on the interplay between tumor-associated macrophages and tumor microenvironment: from mechanism to intervention.Theranostics · 2025Review
- Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.Frontiers of medicine · 2024Review
- Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer.Biochemical and biophysical research communications · 2024Review
- Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity.Nature metabolism · 2024Article
- Adipose Tissue Analysis Toolkit (ATAT) for automated analysis of adipocyte size and extracellular matrix in white adipose tissue.Obesity (Silver Spring, Md.) · 2024Article
- Whole-Mount Imaging of Adipose Tissue Macrophages.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Alterations in the mammary gland and tumor microenvironment of formerly obese mice.BMC cancer · 2023Article
- Blockade of TGF-β signalling alleviates human adipose stem cell senescence induced by native ECM in obesity visceral white adipose tissue.Stem cell research & therapy · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.