Investigating the link between epithelial-mesenchymal transition and the cancer stem cell phenotype: A mathematical approach
Abstract
Under the cancer stem cell (CSC) hypothesis, sustained metastatic growth requires the dissemination of a CSC from the primary tumour followed by its re-establishment in a secondary site. The epithelial-mesenchymal transition (EMT), a differentiation process crucial to normal development, has been implicated in conferring metastatic ability on carcinomas. Balancing these two concepts has led researchers to investigate a possible link between EMT and the CSC phenotype-indeed, recent evidence indicates that, following induction of EMT in human breast cancer and related cell lines, stem cell activity increased, as judged by the presence of cells displaying the CD44(high)/CD24(low) phenotype and an increase in the ability of cells to form mammospheres. We mathematically investigate the nature of this increase in stem cell activity. A stochastic model is used when small number of cells are under consideration, namely in simulating the mammosphere assay, while a related continuous model is used to probe the dynamics of larger cell populations. Two scenarios of EMT-mediated CSC enrichment are considered. In the first, differentiated cells re-acquire a CSC phenotype-this model implicates fully mature cells as key subjects of de-differen...Continue Reading
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