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Enteritis increases risk of bowel cancer

Microscopic image of a tissue section through a bowel tumour

Microscopic image of a tissue section through a bowel tumour with special dye: the cells that are dyed blue produce the growth factor epiregulin. Most of the cells are supporting cells (tumour fibroblasts). (Image: Dr. Clemens Neufert)

Supporting cells are the starting point for effective medicinal cancer treatment

A connection between enteritis and bowel cancer has long been suspected. Now a team of researchers under the leadership of the Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology (Director: Prof. Dr. Markus F. Neurath) of Universitätsklinikum Erlangen (Erlangen University Hospital) has been able to prove that certain supporting cells form important links between enteritis and bowel cancer. In an inflamed environment, these cells, known as tumour fibroblasts, promote the production and release of the key protein and growth factor epiregulin, which can actively accelerate the growth of bowel cancer cells. The findings by the group of scientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) led by Dr. Clemens Neufert and Prof. Neurath were recently published in the April edition of the American Journal of Clinical Investigation 1 (and previously published online).

Bowel cancer is one of the most common malignant diseases in the Western world. Despite advances in clinical diagnostics and therapy, patients only have a chance to recover if the disease is detected at an early stage. Chronic or recurrent intestinal infections constitute a risk factor for the development of bowel cancer. ‘The starting point for our work was a series of extensive analyses of tumour tissue, which included an automated examination of all genetic activity in different types of bowel cancer tumours. This resulted in a long list of genes that were potentially interesting candidates, which we analysed further,’ the Erlangen team of researchers describes the early stages of the project. ‘After a while the signs were pointing to epiregulin playing an important role in bowel cancer growth,’ the scientists say. The new insights were surprising, as so far it had only been known that a lack of epiregulin exacerbates infection reactions in the intestine. Increased production of epiregulin was therefore expected to inhibit tumour growth rather than stimulate it.

Discovery of an improved approach to medicinal bowel cancer therapy

After several years of joint research, the Erlangen bowel researchers and scientists from Bayreuth, Mainz, Munich, and North Carolina (USA), have succeeded in clearly defining the functional role epiregulin plays in infection-dependent tumour development: the researchers discovered a molecular mechanism between intestinal infections and infectin-dependent bowel cancer growth. ‘Our laboratory results are impressive as they reveal that epiregulin plays a dual role. On the one hand it supports tissue repair in the intestine in case of ulcerous infection reactions, on the other hand it promotes the growth of bowel cancer,’ Dr. Neufert and Prof. Neurath explain.

In addition, the researchers were able to identify the cell type responsible for epiregulin production: it is produced by supporting cells known as tumour fibroblasts. They are able to produce large amounts of epiregulin in an inflamed environment, and may even stimulate other cells to produce the growth factor. Now Dr. Neufert and Prof. Neurath hope that therapeutic measures for the treatment of bowel cancer can be improved on the basis of their findings.

1) C. Neufert, C. Becker, Ö. Türeci, M. J. Waldner, I. Backert, K. Floh, I. Atreya, M. Leppkes, A. Jefremow, M. Vieth, R. Schneider-Stock, P. Klinger, F. R. Greten, D. W. Threadgill, U. Sahin, M. F. Neurath (2013): Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasias through ERK. J Clin Invest Volume 123, issue 4 (Apr 2013)).

Further information:

Dr. Clemens Neufert
Phone: +49 (0)9131 85 45062
clemens.neufert@uk-erlangen.de

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