Mammary ductal elongation and myoepithelial migration are regulated by the composition of the extracellular matrix

K. V. Nguyen-Ngoc, Andrew Ewald

Research output: Contribution to journalArticle

Abstract

Mammary branching morphogenesis occurs over a period of weeks deep inside an adipocyte-rich stroma. The adipocytes contain light-scattering lipid droplets that limit the depth of penetration of visible light. Organotypic culture methods were developed to enable high-resolution optical monitoring of branching morphogenesis ex vivo. A challenge has been to identify the best culture conditions to model specific developmental events. We recently demonstrated that collagen I induces protrusive invasion in both normal and neoplastic mammary epithelium. In this study, we observed that the abundance of collagen I fibrils correlated strongly with invasive behaviour, even when the collagen I concentration was identical. We found that the extent of fibril assembly was experimentally manipulable by varying the incubation time at 4°C following pH neutralization. We next tested the capacity of collagen I fibrils to induce invasive behaviour when presented in combination with basement membrane proteins (Matrigel). We found that epithelial organoids in mixed gels of collagen I and basement membrane proteins exhibited more extensive branching morphogenesis but did not initiate protrusions into the matrix. Organoids in pure Matrigel produced many small epithelial buds that were bare of myoepithelial cells. Surprisingly, organoids in mixed gels of collagen I and Matrigel produced fewer epithelial buds, the buds elongated further, and the elongating buds remained covered by myoepithelial cells. Our mixed gels therefore provide a more physiologically accurate model of mammary branching morphogenesis. Our results also suggest that changes in the composition of the extracellular matrix could induce migration of epithelial cells past myoepithelial coverage.

Original languageEnglish (US)
Pages (from-to)212-223
Number of pages12
JournalJournal of Microscopy
Volume251
Issue number3
DOIs
StatePublished - Sep 2013

Fingerprint

Extracellular Matrix
Breast
Collagen
Organoids
Morphogenesis
Gels
Adipocytes
Basement Membrane
Membrane Proteins
Light
Epithelium
Epithelial Cells
matrigel

Keywords

  • Basement membrane
  • Collagen I
  • Extracellular matrix
  • Mammary branching morphogenesis

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Mammary ductal elongation and myoepithelial migration are regulated by the composition of the extracellular matrix. / Nguyen-Ngoc, K. V.; Ewald, Andrew.

In: Journal of Microscopy, Vol. 251, No. 3, 09.2013, p. 212-223.

Research output: Contribution to journalArticle

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