A single dividing cell population with imbalanced fate drives oesophageal tumour growth
Julia Frede, Philip Greulich, Tibor Nagy, Benjamin D. Simons & Philip H. Jones, Nature Cell Biology (2016) DOI:10.1038/ncb3400 [Published online 22 August 2016]
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In this work combining genetic lineage tracing with biophysical modelling, Ben Simons' group examined the patterns of cell division in a mouse model of oesophageal cancer. They found a surprising result: tumour growth was not driven by faster cell division in a subset of 'cancer stem cells', but by a subtle increase in production of dividing cells over non-dividing cells. If the same mechanisms are shown to underlie tumour development in humans, this insight offers a potential new strategy for blocking tumour growth by targeting imbalanced cell fate.
Abstract from paper:
Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium.
However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by KrasG12D expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity.
Abstract reprinted by permission from Macmillan Publishers Ltd: Nature Cell Biology, advance online publication, 22 August 2016 (DOI:10.1038/ncb3400)
Figure adapted by permission from Macmillan Publishers Ltd: Nature Cell Biology, (DOI:10.1038/ncb3400), copyright 2016.
See also this news article from Cancer Research UK.
Read more about research in the Simons lab.