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Blocked fibroblast signalling to intestinal stem cells reduces tumour growth

Thu, 04/02/2020 - 11:21
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Scientists at Yale and collaborators in Greece have identified a tightly sequestered group of stem cells within the intestine as suspects in the development of colon cancer and report that unprepossessing neighbours of stem cells actually harbour a molecular villain that can jump-start cancers of the colon.

The study, 'Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche', published in Nature, may help to explain exactly how genetic mutations within those stem cells can cause tumours of the digestive track.

The tightly packed group of stem cells within the intestine are surrounded by fibroblasts, which help form connective tissue and are one of the most common cell types in the body. Dr Manolis Roulis, associate research scientist in the lab of Richard Flavell, Sterling Professor of Immunobiology, found that a rare form of fibroblast expressing Cox-2 enzymes directs communication with intestinal stem cells. When they blocked signals from this fibroblast to intestinal stem cells in mice with colorectal cancer, tumours were reduced by 50%.

A staining for a marker of fibroblasts (purple cells) which surround epithelial cells (green) in a mouse intestine. This is the place where tumours initiate. (Credit: Yale University)
A staining for a marker of fibroblasts (purple cells) which surround epithelial cells (green) in a mouse intestine. This is the place where tumours initiate. (Credit: Yale University)

Intriguingly, the authors said, this same communication is also blocked by aspirin and other anti-inflammatory drugs, which have previously been shown to have a protective effect against development of colorectal cancers.

"We also found that blocking this same cellular communication has a dramatic effect on the interactions of fibroblasts and stem cells in human systems we studied in the lab," explained Roulis.

Roulis said the findings could help researchers develop new specific drugs to prevent colon cancer in those at risk without the side effects of aspirin and other inhibitors of this pathway currently used as anti-inflammatory drugs.

To access this paper, please click here