Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells
- Ecole Polytechnique Federale de Lausanne (Switzerland). Inst. of Bioengineering
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.
Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC)
- DOE Contract Number:
- AC02-05CH11231
- OSTI ID:
- 1212110
- Report Number(s):
- LBNL-6059E
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, Issue 8; ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
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