Obesity enhances local myofibroblast content and stiffness-promoting extracellular matrix (ECM) components in mammary adipose tissue, according to an experimental study published in Science Translational Medicine.
Bo Ri Seo, from Cornell University in Ithaca, N.Y., and colleagues examined whether obesity and ECM density are functionally linked in breast cancer.
The authors used mouse models to examine whether obesity enhances local myofibroblast content in mammary adipose tissue and whether these changes enhance interstitial ECM stiffness.
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The researchers found that myofibroblasts and stiffness-promoting ECM components were enriched in mammary fat of both diet- and genetically-induced mouse models of obesity.
These alterations correlated with varied adipose stromal cell (ASC) characteristics; compared with ASCs from lean control mice, ASCs isolated from obese mice contained more myofibroblasts and deposited denser and stiffer EMCs.
Mechanosignaling was stimulated by decellularized matrices from obese ASCs, affecting the malignant potential of breast cancer cells.
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The findings were supported by analysis of specimens from obese breast cancer patients, and the observation that in a mouse model, caloric restriction reduced myofibroblast content in mammary fat.
“Collectively, these findings suggest that obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering mammary ECM mechanics with important potential implications for anticancer therapies,” the authors write.
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