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PETBioNewsNewsNeighbour cells implicated in colorectal cancer

BioNews

Neighbour cells implicated in colorectal cancer

Published 3 April 2020 posted in News and appears in BioNews 1042

Author

Dr Nicoletta Charolidi

Image by Sílvia Ferreira, Cristina Lopo and Eileen Gentleman via the Wellcome Collection. Depicts a single human stem cell embedded within a porous hydrogel matrix (false colour).
CC BY 4.0
Image by Sílvia Ferreira, Cristina Lopo and Eileen Gentleman via the Wellcome Collection. Depicts a single human stem cell embedded within a porous hydrogel matrix (false-coloured cryogenic scanning electron micrograph).

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...

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.

Sources and References

  • 01/04/2020
    Yale News
    Suspect cells' 'neighbour' implicated in colorectal cancer
  • 01/04/2020
    Nature
    Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche

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