Mammary ECM composition and function are altered by reproductive state
Article first published online: 1 OCT 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 41, Issue 4, pages 207–220, December 2004
How to Cite
Schedin, P., Mitrenga, T., McDaniel, S. and Kaeck, M. (2004), Mammary ECM composition and function are altered by reproductive state. Mol. Carcinog., 41: 207–220. doi: 10.1002/mc.20058
- Issue published online: 23 OCT 2004
- Article first published online: 1 OCT 2004
- Manuscript Accepted: 16 AUG 2004
- Manuscript Revised: 26 JUL 2004
- Manuscript Received: 26 MAY 2004
To address whether reproductive state alters mammary gland extracellular matrix (ECM) composition and function, ECM was isolated from nulliparous, pregnant, lactating, involuting, and regressed rat mammary glands. The ECM composition of fibronectin, tenascin, laminin, clusterin, and MMPs was found to vary dramatically with reproductive state. In 3-dimensional (3-D) culture, we identified novel effects of these endogenous mammary matrices on mammary epithelial cells. Specifically we found that (1) matrix isolated from nulliparous animals promoted the formation of epithelial ducts with bifurcation, (2) matrix isolated from mid-involuting mammary glands induced cell death, (3) matrix isolated from late-stage involuting glands restored glandular development, while (4) matrix isolated from parous animals restricted glandular morphogenesis. Our data were consistent with mammary gland ECM facilitating epithelial cell proliferation, differentiation, death, and glandular reorganization that occur during the pregnancy and involution cycle. Further, we show that the parous gland has persistent changes in ECM function. Cumulatively, our data demonstrated that the microenvironment of the normal adult mammary gland is highly plastic, which has important implications for mammary tumor cell progression and dormancy. These data also raised the possibility of targeting mammary matrix production with preventive or therapeutic interventions. © 2004 Wiley-Liss, Inc.