Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

Jordi Alcaraz, Ren Xu, Hidetoshi Mori, Celeste M. Nelson, Rana Mroue, Virginia A. Spencer, Doug Brownfield, Derek C. Radisky, Carlos Bustamante, Mina J. Bissell

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

In the mammary gland, epithelial cells are embedded in a 'soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for β-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of β-casein expression required both laminin signalling and a 'soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of β-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues' unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2829-2838
Number of pages10
JournalEMBO Journal
Volume27
Issue number21
DOIs
StatePublished - Nov 5 2008
Externally publishedYes

Keywords

  • β1-integrin
  • Atomic force microscopy
  • Laminin
  • Microenvironment
  • Tissue elasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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