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  6. Cancer cells 'move out' to escape regulatory neighbours

Cancer cells 'move out' to escape regulatory neighbours

March, 2012

Cancer is the name given to illnesses that involve the growth of tumours, which can develop from any cell type in the body. The development of a tumour starts when just one cell, or a small group of cells, starts to multiply uncontrollably. Genetic alternations may not be enough to explain how cells proliferate, manage to survive, and escape the regulatory signals from other surrounding cells that would normally limit cell growth. The impact of cell organisation around mutant cells is an area of study that could increase the understanding of cancer development.

Leung and Brugge have reproduced the early stages of tumour development in a 3-dimensional cell culture system. Using MCF10A non-transformed human mammary epithelial cells the authors were able to grow polarised growth arrested acinar structures with a hollow lumen on a reconstituted basement membrane. They then modelled oncogene induction in single cells within these 3-dimensional acini to study how sporadic mutant cells develop within organised epithelial cells. It was found that single cells over-expressing ERBB2 dissociated from the epithelial layer and translocated to the lumen. Blocking cell proliferation did not inhibit translocation but blocking translocation prevented clonal outgrowth. The authors observed compromised basement membrane in the area with ERBB2 over-expressing cells leading them to propose that translocation is triggered by a disturbance of local cell-matrix adhesion. Results suggest that ERBB2-mediated clonal expansion involves an initial cell translocation, which allows cells to escape the regulatory environment of epithelial cells. Studies were carried out using Nikon A1 & C1 confocal microscopes, and Nikon Ti-E inverted microscope with CSU-X1 spinning disk confocal from the Nikon Imaging Centre at Harvard Medical School.

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