How breast cell communities organise to form tissue

A new study by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) of the different types of cells that make up the human breast shows that not only do cells possess an innate ability to self-organise into communities, but these communities of different types of cells can also organise themselves with respect to one another to form and maintain healthy tissue.

Understanding this ability of different types of cell communities to self-organise into tissue may help explain how the processes of stem cell differentiation and tissue architecture maintenance are coordinated. It might also lead to a better understanding of what goes wrong in cancer.

Mark LaBarge, a cell and molecular biologist in Berkeley Lab's Life Sciences Division, and Mina Bissell, a Berkeley Lab Distinguished Scientist also with the Life Sciences Division, carried out a unique study of normal human mammary epithelial cells that had been enriched into pools of the two principal lineages that make up breast tissue - the milk-producing luminals and the myoepithelials that blanket them. In healthy breast tissue, these two lineages organise themselves into an ordered bi-layer.

To observe and quantify changes in the distribution of these cell lines with respect to one another over time, LaBarge, Bissell and a team of collaborators used a unique "micropatterning" technique, in which the cells were confined to a three-dimensional cylindrical geometry.

"We demonstrated that while bi-layered organisation in mammary epithelium is driven mainly by the lineage-specific differential expression of the E-cadherin adhesion protein, the expression of the P-cadherin adhesion protein makes additional contributions that are specific to the organisation of the myoepithelial layer," LaBarge says.

"Disruption of these adherens junction proteins or the actomyosin network that supports them either prevented the formation of the bi-layer, or caused a loss of pre-formed bi-layers. This is the first reported evidence that the two principle lineages of adult human mammary gland possess intrinsic and reversible characteristics that guide their organisation into a bi-layer."

The findings have been reported in a paper published in the Proceedings of the National Academy of Science.