Mammary Gland ECM Remodeling, Stiffness, and Mechanosignaling in Normal Development and Tumor Progression
- 1Department of Medicine, Division of Medical Oncology, University of Colorado, Denver, Colorado 80045
- 2University of Colorado Cancer Center, Denver, Colorado 80045
- 3Department of Pharmacology and Laboratory for Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706
- Correspondence: pjkeely{at}wisc.edu
Abstract
Cells of the mammary gland are in intimate contact with other cells and with the extracellular matrix (ECM), both of which provide not only a biochemical context, but a mechanical context as well. Cell-mediated contraction allows cells to sense the stiffness of their microenvironment, and respond with appropriate mechanosignaling events that regulate gene expression and differentiation. ECM composition and organization are tightly regulated throughout development of the mammary gland, resulting in corresponding regulation of the mechanical environment and proper tissue architecture. Mechanical regulation is also at play during breast carcinoma progression, as changes in ECM deposition, composition, and organization accompany breast carcinoma. These changes result in stiffer matrices that activate mechanosignaling pathways and thereby induce cell proliferation, facilitate local tumor cell invasion, and promote progression. Thus, understanding the role of forces in the mammary gland is crucial to understanding both normal developmental and pathological processes.
Footnotes
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Editors: Mina J. Bissell, Kornelia Polyak, and Jeffrey Rosen
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Additional Perspectives on The Mammary Gland as an Experimental Model available at www.cshperspectives.org
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