Age-dependent matrisome remodeling in young breast adipose tissue identifies a potential mechanism of tumor aggressiveness

The extracellular matrix (ECM) is a dynamic regulator of breast tissue homeostasis and plays a critical role in breast cancer progression.Across the lifespan, breast tissue undergoes extensive remodeling that drives changes in ECM architecture, deposition, and matrisome composition. These changes underlie age-differences observed in disease development, clinical outcome, and tumor aggressiveness. In young (<40 years) breast tissue, ECM protein deposition is more abundant, and collagen fibers are thicker and more aligned compared to aged tissue. Features of aged mammary tissue have been linked to aggressive disease in vivo ; however, murine tissues are physiologically distinct from human tissue and do not fully recapitulate the complex interactions between the tumor and its microenvironment. To date, age-dependent ECM remodeling in human breast adipose tissue remains poorly defined., highlighting the need for primary models of ECM and breast aging. To address this need and to identify ECM proteins driving aggressive breast cancer phenotypes, we performed protein profiling of healthy breast adipose tissue from aged (>50) and young (<40) women, combined with analyses of ECM and tissue architecture. Contrary to existing findings, we observed no difference in total collagen composition via Masson's trichrome staining and rheological measures of stiffness between the aged and young tissues. However, proteomic analysis revealed increased expression of collagen types I, IV, V, and XV in young women, consistent with existing studies published by others in mouse mammary tissue. Periostin (POSTN) expression, a matricellular protein required for the wound healing response and collagen synthesis, was elevated in the young breast adipose. Additionally, data mining from RNA-Seq of human tumor samples uncovered that POSTN expression increases with proximity to tumor tissue and is enriched in hormone receptor positive cancers. Taken together, these data demonstrate that the ECM in the breast adipose is age-specific and that shifts in collagen content and ECM regulators, such as POSTN, may contribute to aggressive breast cancer in young women.