Journal
EMBO JOURNAL
Volume 27, Issue 21, Pages 2829-2838Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2008.206
Keywords
atomic force microscopy; beta 1-integrin; laminin; microenvironment; tissue elasticity
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Funding
- Department of Energy [DE-AC03-76SF00098]
- National Institutes of Health [CA64786, CA57621, GM-071552]
- Department of Defense (Innovator Award to MJB)
- Catalonian Ministry of Universities, Research and Information Society
- Canadian Institute for Health Research
- Susan G Komen Breast Cancer Foundation
- American Cancer Society
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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 beta-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of beta-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 beta-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.
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