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Stem cell changes link high-fat diet to colon cancer

07 March 2016

By Paul Waldron

Appeared in BioNews 842

A study in mice has shown that a diet high in fat can stimulate the production of stem cells in the intestine, which might then go on to form tumours. The findings could explain the link between obesity and an increased risk of colorectal cancer.

Obesity has been associated with an increased risk of developing several types of cancer, including oesophageal, breast and colon cancer, but it is not clear what processes underlie these associations.

Intestinal stem cells are able to differentiate in any of the cell types which make up the lining of the gut. However, since stem cells can reproduce themselves indefinitely, they are thought to be more at risk of developing into cancer cells.

In the study, published in Nature, mice that were on a high-fat diet containing 60 percent fat for nine to 12 months produced many more intestinal stem cells than did the mice in the control group.

The researchers also found that another group of cells, called progenitor cells, which are produced by stem cells, were themselves showing stem-cell characteristics. When the researchers cultured these cells in the laboratory, they were found to be able to develop into mini-intestines.

'This is really important because it's known that stem cells are often the cells in the intestine that acquire the mutations that go on to give rise to tumours,' said Dr Ömer Yilmaz, a cancer biologist at MIT's Koch Institute for Integrative Cancer Research in Boston, Massachusetts, and a lead author of the study.

'Not only do you have more of the traditional stem cells [on a high-fat diet], but now you have non-stem-cell populations that have the ability to acquire mutations that give rise to tumours,' he said.

The high-fat diet appeared to activate a pathway governed by a fatty-acid sensor called PPAR-delta. This protein acts by allowing cells to burn fat to produce energy, while also turning on several genes that are active in stem cells. When the researchers treated mice with a drug that stimulates PPAR-delta, they found similar effects on gut stem cells as they did during the high-fat diet.

Researchers hope that identifying the involvement of PPAR-delta could be useful in determining the cancer risk of patients who have increased activity in this pathway. Professor Kay Lund, a cell biologist from the University of North Carolina, who was not involved in the study, told Nature News: 'It could provide an opportunity to give those patients an earlier intervention.'

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