Researchers have challenged conventional thinking on how the bowel lining develops and, in the process, suggested a new mechanism for how bowel cancer starts. The researchers produced evidence that stem cells are responsible for maintaining and regenerating the ‘crypts’ that are a feature of the bowel lining, and believe these stem cells are involved in bowel cancer development, a controversial finding as scientists are still divided on the stem cells’ existence.
Bowel cancer is a leading cause of cancer-related death in the developed world. Professor Burgess said the research findings suggested although ‘crypt-generating’ stem cells were usually ‘quiet’ in a healthy bowel, they were likely to be the initiators of bowel cancer.
The critical change that led the stem cells to initiate out-of-control budding was likely related to the APC (adenomatous polyposis coli) gene, Professor Burgess said. “Eighty-five per cent of all bowel cancers have lost APC function, and all have excessive crypt budding,” he said. “APC is essential for controlling crypt production and maintaining adhesion between bowel stem cells. Losing APC disturbs control of bowel stem cell location and production, causing ‘chaotic’ growth of crypt buds and leading directly to precancerous and cancerous growths.”
Professor Burgess said the research, combined with recent studies from institute researchers Dr Michael Buchert and Associate Professor Matthias Ernst, provided strong evidence that crypt-generating stem cells were responsible for driving bowel cancer growth.
“It is essential to know whether these stem cells are driving or maintaining cancer development, as they behave very differently to other bowel stem cells,” Professor Burgess said. “To target bowel cancer effectively, we need to think differently about how to kill stem cells that have lost the APC gene.”
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