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Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype
Gokhan Bahcecioglu1, Xiaoshan Yue1, Erin Howe2,3
1Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN, 46556, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 7, 2021
Summary
Aging breast tissue extracellular matrix (ECM) drives normal cells toward a cancer-like state, increasing invasiveness and motility. Targeting ECM aging may offer new cancer prevention and treatment strategies.
Area of Science:
- Biomedical Science
- Cancer Biology
- Cellular Aging
Background:
- Age is a primary cancer risk factor, with genetic changes well-studied.
- The role of the aging extracellular matrix (ECM) in cancer progression remains largely unexplored.
Purpose of the Study:
- To investigate the impact of aging breast ECM on mammary cell behavior.
- To determine if aging ECM alone can induce a cancer-like phenotype.
Main Methods:
- Decellularized aged and young mouse breast ECM were used.
- Normal human mammary epithelial cells (KTB21) and invasive breast cancer cells (MDA-MB-231) were cultured on these matrices.
- Lysyl oxidase (LOX) knockdown was performed to assess its role.
Main Results:
- Aging ECM induced invasive and cancer-like phenotypes in KTB21 cells, increasing motility and invasion.
- Aged ECM caused loss of E-cadherin localization, elevated inflammatory cytokines, and upregulated cancer-related genes.
- LOX knockdown reversed aged ECM-induced changes, restoring E-cadherin, reducing invasion, and decreasing cytokine production.
Conclusions:
- The aging breast ECM contains biochemical, physical, and mechanical cues that promote invasive behavior in mammary cells.
- This study highlights the aging ECM as a significant, previously overlooked factor in cancer development.
- Understanding cell-ECM interactions in aging may reveal novel therapeutic targets for cancer prevention and treatment.
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