Trigger points for bowel cancer found at a young age

Regenerative stem cells as the origin of inflammation-associated intestinal tumors

03-Jul-2024

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If you ask a cell biologist how cancer develops, the answer is: through a mutation in a stem cell. In a new publication in the journal "Nature Genetics", scientists from the Erasmus Medical Center (Erasmus MC) in Rotterdam and the Philipps University of Marburg break this dogma. They show that an intestinal tumor can also develop from a specialized cell type that actually has the task of producing mucus or antibacterial molecules.

The researchers came to this discovery because of a contradiction. The main risk factors for colon cancer, namely chronic inflammation and western dietary habits, the so-called western-style diet, lead to the normal stem cells being suppressed. However, if this is the case, they cannot be the origin of the colon tumors. Earlier studies by Dr. Mark Schmitt, a pharmacologist from Marburg and head of a research group at the Institute of Pharmacology at Philipps University, who was involved in the work, show that intestinal cells that actually specialize in other tasks revert to a stem cell-like cell type in response to inflammation-induced tissue damage in order to regenerate the intestinal tissue. Could the specialized intestinal cell then be the origin of intestinal tumours that develop in connection with inflammation?

This hypothesis proved to be correct. In mice with a genetic predisposition for cancer in specialized intestinal cells, tumours developed as soon as the intestine became inflamed. The origin of these intestinal tumors was not a stem cell, but the specialized intestinal cell, as the researchers showed.

Then the researchers noticed something else: the intestinal tumors of the mice not only resemble the tumors that occur in people with chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, but also the intestinal tumors of people who do not suffer from such a disease. With the help of machine learning and artificial intelligence, the study was able to show that around 40 per cent of human intestinal tumors originate in a specialized intestinal cell.

This figure is much higher than the researchers had expected and is probably due to a mild but persistent chronic inflammation that can be caused in the gut by Western dietary habits. As Dr. Schmitt's research group was able to show, the consumption of a Western-style diet similarly leads to a loss of stem cells and the activation of specialized cells that could then grow into a tumor. This does not only happen in the relatively small group of bowel cancer patients with inflammatory bowel disease, but in many more people.

The researchers link their findings to a worrying development: Bowel cancer, by definition a disease associated with age, is increasingly being diagnosed in young people. The results now confirm the researchers' suspicion that there is a link between Western lifestyle, chronic inflammation and the development of colorectal cancer at a young age, possibly related to the alternative cells of origin of colorectal tumors studied.

Their findings are also important because they could lead to a new classification of colon cancer, the researchers argue: colorectal tumors that arise from specialized cells have a worse prognosis than tumors that arise from intestinal stem cells. The researchers hope that the updated classification will lead to better prediction of disease progression and personalized treatments.

Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.

Original publication

Mathijs P. Verhagen, Rosalie Joosten, Mark Schmitt, Niko Välimäki, Andrea Sacchetti, Kristiina Rajamäki, Jiahn Choi, Paola Procopio, Sara Silva, Berdine van der Steen, Thierry P. P. van den Bosch, Danielle Seinstra, Annemarie C. de Vries, Michail Doukas, Leonard H. Augenlicht, Lauri A. Aaltonen, Riccardo Fodde; "Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation"; Nature Genetics, 2024-6-20

https://www.bionity.com/en/news/1183865/trigger-points-for-bowel-cancer-found-at-a-young-age.html