Differences in the way stem cells divide provide clues about bowel cancer

In collaboration with Adfero

Changes in the way that stem cells divide in the gut could lead to cancer, according to a new study funded by the Bobby Moore Fund for Cancer Research UK.

The team of scientists from the University of Dundee have found that structures called mitotic spindles, which separate genetic material during the process of cell division, line up in stem cells in different ways within normal and pre-cancerous tissues.

Three-dimensional images of these mitotic spindles revealed that they behaved abnormally in tissue with a fault in the APC gene, which is associated with bowel cancer.

Stem cells divide to produce one daughter that is also a stem cell and another that is more specialised. They also double up their DNA and divide the copies among the two daughter cells.

Normally, the specialised daughter gets the copied DNA while the stem cell daughter keeps the original version that is unlikely to contain cancer-causing errors. This asymmetric split happens thanks to the spindles, which line up in a specific direction.

But in pre-cancerous tissues, the spindles line up randomly. So the stem cells sometimes inherit the copied DNA, which could contain errors that take these cells one step closer to cancer.

Lead researcher Professor Inke Näthke, from the newly launched Dundee Cancer Centre, said: "Using this technique, we found that this process of asymmetric division in stem cells is lost in tissue that gives rise to cancers in the gut, so these spindles behave differently in pre-cancerous tissue.

"This is important as it may have implications in developing techniques for identifying pre-cancerous tissue at an early stage when it still appears normal, giving clinicians a chance to catch the disease in the early stages of development.

"It might also have implications for the types of treatment that should be considered," he added.

The research, which is published in the journal Cell Stem Cell, also involved scientists from the Beatson Institute for Cancer Research in Glasgow and The Netherlands.

"This is a perfect example of the kind of cross-disciplinary work we expect to be doing under the auspices of the new Dundee Cancer Centre launched last week with Cancer Research UK," said Professor Nathke.

"We have combined expertise in imaging, pathology, surgery and cellular science to make these findings."

References

  • Quyn, A., Appleton, P., Carey, F., Steele, R., Barker, N., Clevers, H., Ridgway, R., Sansom, O., & Näthke, I. (2010). Spindle Orientation Bias in Gut Epithelial Stem Cell Compartments Is Lost in Precancerous Tissue Cell Stem Cell, 6 (2), 175-181 DOI: 10.1016/j.stem.2009.12.007