Plasticity of epithelial cell boundaries governed by EGF and actin remodelling

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The tissue cells in our body respond to circulating factors, amongst them so-called growth factors, by undergoing changes in shape, movement or division rates. One of the most important growth factors is called EGF and it binds to its own receptor to convey the instructions necessary for these changes to the interior of the cell. In some cancer types, this receptor can be altered such that it continuously demands these types of changes from the cell; i.e. it forces the cell to grow and divide abnormally, extract itself from the tissue boundaries and move to another site. It follows that drugs, which inhibit this receptor are of widespread interest and a major focus of pharmaceutical companies.We have studied normal, non-cancerous breast cells that can routinely be grown in petri dishes in the presence of growth factors including EGF. These breast cells form a continuous sheet, but within this sheet, cells remain able to roam around. However when we remove the EGF, these cells project long, finger-like protrusions into each other, which we call "interdigitations". In these interdigitated sheets, cell positions are fixed like the pieces of a completed jigsaw puzzle. If we add fresh EGF to this mesh of interdigitated cells, the finger-like protrusions disappear and the cells start to move around again. Such interdigitations are in fact common in tissues that have to endure mechanical stress. They may help to give the tissue superior flexibility and strength to withstand, for example, changes in volume in breast tissue due to lactation. Our work has defined an experimental set-up in which we can study the proteins that respond to the EGF receptor and mediate this reversible remodeling process. New insights that will be gained from this work may help to inform both on the mechanism by which normal tissues increase their strength but also on disease states in which tissue boundaries are compromised due to a deregulation of the proteins involved.