The maintenance of epithelial tissue requires a fine balance between growth and cell death. Little is known about the control mechanisms that ensure this balance, which when deregulated likely contribute to the development of cancer.
Now, an interdisciplinary team from UCL has found that mechanical forces squeeze excess cells out of overcrowded healthy tissue in order to maintain the correct tissue size.
Researchers from the MRC Laboratory of Molecular Cell Biology, Professor Tom Duke and Aida Mehonic from the London Centre for Nanotechnology and the UCL Ear Institute used a combination of fluorescence imaging, laser dissection and computer modelling to identify a novel process of compression-induced extrusion of cells that counterbalances growth. The removal of dying cells from tissue has been described previously, but this new process has a different mechanical signature and, importantly, is independent of cell death. Live cells are increasingly squeezed by their neighbours until they pop out of the tissue. The new finding has implications for our understanding of the early stages of cancer, since cells extruded from a developing tumour that fail to die will be free to go on to form metastases.
The study, published in Nature, is one of the first direct demonstrations of a role for mechanics in tissue homeostasis.
Figure: The coloured cells in this overcrowded epithelial tissue are ultimately expelled