Mammary ECM Composition and function are altered by reproductive state

Pepper Schedin, Terry Mitrenga, Shauntae McDaniel, Mark Kaeck

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalMolecular Carcinogenesis
Volume41
Issue number4
DOIs
StatePublished - Dec 2004
Externally publishedYes

Keywords

  • Clusterin
  • Fibronectin
  • Laminin
  • Metalloproteinases
  • Tenascin

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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