Obesity reduces mammary epithelial cell TGFβ1 activity through macrophage‐mediated extracellular matrix remodeling

Autor: Lauren E. Hillers-Ziemer, Brenna N. Walton, Tamara Chamberlin, Victoria Thompson, Lisa M. Arendt
Rok vydání: 2020
Předmět:
0301 basic medicine
mammary gland
obesity
Decorin
Mammary gland
Mice
Obese
Biochemistry
Extracellular matrix
Mice
0302 clinical medicine
Tumor Microenvironment
Medicine
Macrophage
Breast
skin and connective tissue diseases
Cells
Cultured
Research Articles
decorin
transforming growth factor beta
biology
Stem Cells
Middle Aged
Extracellular Matrix
medicine.anatomical_structure
Female
Research Article
Biotechnology
Adult
Adolescent
Breast Neoplasms
Diet
High-Fat
Transforming Growth Factor beta1
Young Adult
03 medical and health sciences
Mammary Glands
Animal
Breast cancer
Genetics
Animals
Humans
Progenitor cell
Mammary Glands
Human
Molecular Biology
business.industry
Macrophages
Epithelial Cells
Transforming growth factor beta
medicine.disease
Epithelium
Mice
Inbred C57BL
030104 developmental biology
Cancer research
biology.protein
business
030217 neurology & neurosurgery
Zdroj: The FASEB Journal
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.202000228rr
Popis: Obesity is a risk factor for breast cancer in postmenopausal and high‐risk premenopausal women. Changes within the obese breast microenvironment may increase breast cancer risk. Transforming growth factor beta‐1 (TGFβ1) is a major regulator of mammary epithelial stem/progenitor cells, and its activity is dysregulated under conditions of obesity. Using a high‐fat diet model of obesity in mice and breast tissue from women, we observed that TGFβ1 activity is reduced in breast epithelial cells in obesity. Breast ducts and lobules demonstrated increased decorin in the extracellular matrix (ECM) surrounding epithelial cells, and we observed that decorin and latent TGFβ1 complexed together. Under conditions of obesity, macrophages expressed higher levels of decorin and were significantly increased in number surrounding breast epithelial cells. To investigate the relationship between macrophages and decorin expression, we treated obese mice with either IgG control or anti‐F4/80 antibodies to deplete macrophages. Mice treated with anti‐F4/80 antibodies demonstrated reduced decorin surrounding mammary ducts and enhanced TGFβ1 activity within mammary epithelial cells. Given the role of TGFβ1 as a tumor suppressor, reduced epithelial TGFβ1 activity and enhanced TGFβ1 within the ECM of obese mammary tissue may enhance breast cancer risk.
Databáze: OpenAIRE
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