An investigation into entotic behaviour of breast cancer cellsTools ZAILAN, YASMEEN (2018) An investigation into entotic behaviour of breast cancer cells. MRes thesis, University of Nottingham.
AbstractOver the past decade, a new form of cell-in-cell structure (CICs) known as “entosis” has been described. Entosis is the live engulfment or active invasion of a neighbouring cell into another cell’s cytoplasm, in which the the engulfing cell is called the “entotic” cell and the one taken up is the “entosed” cell. This process is observed in cultures of both tumour and non-tumourigenic cells, but when it occurs in the context of a tumour, it is unclear whether entosis suppresses or promotes cancer progression. There are three known fates of the entosed cell: 1) it can remain viable and proliferate; 2) it can die within the cytoplasm of the entotic cell; or 3) it can escape. Meanwhile, the fate of entotic cell is either survival, which could facilitate oncogenesis, or death, and therefore tumour suppressive. Here, we have investigated the behaviour of breast cancer cells exhibiting entosis using live fluorescence imaging in cells labelled with cortactin- mcherry and nucblue to observe the cell cytoskeleton and nuclei respectively. We have characterized the phenotypes and cell preferences in both monoculture where only “homotypic” entosis can occur, and in co- culture with colorectal cancer cells to determine whether “heterotypic” entosis is feasible. The first hypothesis in this study was that homotypic and heterotypic entosis could be tumour suppressive. A second hypothesis was that p53 signalling could be reactivated in a breast cancer cell (MDA- MB231) after an act of heterotypic entosis with a p53 positive cell. The data obtained suggest that the breast cancer cell line, MDA-MB231 can exhibit homotypic and heterotypic entosis and that after such an event both the entotic and the entosed cell may die, suggesting that entosis can be tumour suppressing. In addition, as a higher percentage of death was witnessed when entosis happened in co-culturing conditions with p53 positive cells, this suggests that it may be possible to reactivate p53 in an entotic cell after an act of entosis. However, as the number of cells analysed in these experiments was small, more data need to be obtained to support the hypothesis that the increased death seen was due directly to entosis and not a bystander-like effect.
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