Stem cells may 'ignite' bowel cancer development

Dec 18 2008

Cancer Research UK scientists have discovered for the first time that stem cells could be the root cause of bowel cancer, according to a study published in Nature.

Scientists at Cancer Research UK's Beatson Institute for Cancer Research in Glasgow, Cardiff University and the Hubrecht Institute in the Netherlands - isolated stem cells in the bowels of mice and 'knocked out' a gene called APC from them. These damaged stem cells then rapidly started to multiply out of control and to form tumours.

Bowel cancer is the third most common cancer in the UK affecting more than 36,500 people each year. This research could pave the way for new treatments to target damaged stem cells and quench their 'ignition' of the disease.

A stem cell is one that, when it divides, produces two 'daughter' cells. One remains a stem cell, while the other multiplies into the sorts of cells required by its organ to keep it functioning. Previously scientists could not be sure if the cancer causing faults occurred directly to stem cells, or whether 'daughter' cells were the route cause of the tumour. This study provides extremely strong evidence to suggest that most bowel cancers start from stem cells.

Study author Dr Owen Sansom, from Cancer Research UK's Beatson Institute, said: "When we studied the effect of blocking the APC gene in the 'parents' - or stem cells - the results were striking and the cells started to transform within days. It was clear the 'ignition point' for the disease was to be found in the stem cells. Using the same experiment, the daughter cells also developed into tumours, but not nearly as often as the stem cells changed. We are now looking to understand how we can use these results to seek out and destroy stem cells that are lacking the APC gene."

Lead author Professor Hans Clevers, from the Hubrecht Institute said: "We are very excited by these findings but we need to establish whether the stem cells behave the same way in human cancers as they do in mice - and this will form the basis of the next stage of our research. We only looked at the APC gene to understand its onset of bowel cancer - it's likely that other genes also play a role in the progression of the disease."

Dr Lesley Walker, Cancer Research UK's director of cancer information said: "As in most cancers, the cell that the cancer originates from has remained elusive in bowel cancer. So this work is a big leap forward in our understanding of the origins of the disease.

"Bowel cancer is one of the most common forms of cancer so anything that adds to our understanding of the disease is very important work."

To listen to an interview with Dr Sansom click here: http://media.cancerresearchuk.org/media/press/Sansom_171208/Owen_Sansom_Dec08.mp3

*Nick Barker et al, Crypt stem cells as the cells-of-origin of intestinal cancer, Nature, 17 December 2008.

This study looked at the role of stem cells in the small and large intestine. Bowel cancer is the third most common cancer in the UK. Each year more than 36,500 people are diagnosed with bowel cancer in the UK - 100 people every day. Bowel cancer is the second most common cause of cancer death in the UK after lung cancer. Around 16,000 people die of bowel cancer each year in the UK.

This study involved using a drug to activate an enzyme that led to the deletion of the APC gene in mice. The researchers looked at how often the mice developed cancer and compared the results to a control group of mice.