Page URL:

Neighbour cells implicated in colorectal cancer

6 April 2020
Appeared in BioNews 1042

A new study characterising the microenvironment of colorectal cancers has revealed a distinct population of cells, residing next to tumour-initiating stem cells, which themselves promote the start of tumour growth in the colon.

The work, published in Nature, is a collaboration between scientists at Yale School of Medicine, Connecticut, and Alexander Fleming, Biomedical Sciences Research Centre in Greece. 

The study showed that intestinal stem cells are surrounded by a rare neighbouring subpopulation of fibroblasts, which were found to express the enzyme Cox-2. Fibroblasts are cells that typically provide the structural support for surrounding cells.

Cox-2 mediates the production of a signalling molecule called prostaglandin E2. In normal conditions, this molecule has a physiological role, but when a mutation occurs in the stem cells, prostaglandin E2 from the fibroblasts binds to a specific receptor in the neighbouring stem cells and promotes tumour initiation. 

The authors showed the importance of this interaction for tumour formation by abolishing expression of Cox-2 specifically in this subset of fibroblasts in relevant mouse models. The result was a 50 percent reduction in colorectal tumours. 

The study also identified which exact receptor in mutated stem cells is involved in this interaction and verified these findings by replicating them using human samples and cultured organoids

Lead co-author, Dr Manolis Roulis, from Yale said: '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'.

Interestingly, aspirin or other anti-inflammatory drugs can block the Cox-2 interaction, explaining why painkillers have a protective effect in the developments of colorectal cancers. However, their daily use often leads to adverse side effects.

With colorectal cancer being the second most deadly cancer worldwide, comprising 5.8 percent of all cancer deaths, these findings open the road for the development of new drugs that can target this specific pathway, and without the side effects of common painkillers.

Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche
Nature |  1 April 2020
Suspect cells' 'neighbour' implicated in colorectal cancer
Yale News |  1 April 2020
2 March 2020 - by Dr Jay Stone 
A common strain of gut bacteria may drive genetic changes that cause bowel cancer, according to research published in Nature...
12 December 2016 - by Ayala Ochert and Ebtehal Moussa 
Researchers have successfully treated a woman with colon cancer using her own immune cells to target a cancer-causing gene that had previously been considered 'undruggable'...
23 July 2012 - by Dr Kimberley Bryon-Dodd 
The genetic mutations underlying colon and rectal cancer are so similar that these cancers should be classified as one disease, a study suggests. Researchers analysed over 200 tumour samples and also identified genes that could serve as targets for future drug treatments...
Log in to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.