Studies: How Helicobacter infections lead to stomach cancer

Stomach cancer can be caused by bacteria
Bacteria of the genus Helicobacter pylori can be assessed as a potential trigger for stomach cancer. In a recent study, scientists from the Berlin Charité were able to show how infections with the bacterium can be responsible for the development of stomach cancer.

Scientists have recently unraveled the mechanisms by which Helicobacter pylori infections contribute to the development of gastritis. Now researchers at Charité - Universitätsmedizin Berlin have also been able to demonstrate that Helicobacter pylori infections can trigger stomach cancer. The scientists have published their results in the specialist journal "Nature".

Increased cell division in infected tissue
Infections with the gastric bacterium Helicobacter pylori are widespread, according to the Charité, and are considered the most important risk factor for the development of gastric cancer. However, it has so far remained unclear how the Helicobacter infections increase the risk of gastric cancer. "After an infection, there is an increased cell division in the infected tissue due to a mechanism that is still unknown," the scientists explain. The research team around Dr. Michael Sigal and Prof. Dr. Thomas F. Meyer, director at the Max Planck Institute for Infection Biology, has now been able to decode this process for the first time.

Associated with accelerated stem cell regeneration in the gastric glands
It was already known that the glands in the stomach have a particularly high regenerative capacity and are completely replaced every one to two weeks. It remained questionable how bacterial infection can lead to long-term changes under these circumstances. In cooperation with scientists from the Max Planck Institute for Infection Biology in Berlin and the Stanford School of Medicine in California, the research team led by Dr. Michael Sigal from the medical clinic with a focus on hepatology and gastroenterology at the Charité in Berlin is now demonstrating how "a Helicobacter infection can be responsible for the development of gastric cancer." Stem cell regeneration has been established within the gastric glands.

More cells with stem cell potential
According to the researchers, under the influence of the bacteria, the number of cells with stem cell potential increases and with them the risk of a pathological change. "In the base of the glands there are long-lasting stem cells that are constantly generating new cells," explains Dr. Sigal. The aim of the study was to determine their identity and also the processes that control their regeneration. For this purpose, the stem cells of the stomach were examined in an animal model, with the help of sensitive new techniques, molecules in the stomach tissue could be displayed in high resolution. The Charité reports that “it was possible to image molecules that regulate the stem cells and to show their spatial proximity to the stem cell area.

Certain enzymes significantly influence the function of the stem cells
The scientists also used a model of Helicobacter pylori infection that mimicked the first stages of cancer development in humans and carried out experiments using so-called organoids (cell cultures derived from human and animal stem cells directly from the stomach tissue). The characterization of the stem cells showed that there are two different types of stem cells in the stomach. Both are positive for the Axin2 marker. In addition, according to their own statements, the scientists "found that the cells that are located directly below the glands produce a specific molecule called R-spondin 3." This has a significant influence on the function of the stem cells and activates cell division in a subpopulation of the stem cells, which increases the rate of regeneration of the gastric glands.

Bacteria as cancer trigger underestimated so far
According to the researchers, infection with Helicobacter pylori leads to an increase in the production of R-spondin and an increase in stem cell activity, with the suspicion that a long-term increase in stem cell division directly promotes cancer development. While it has long been known that certain viruses can trigger cancer by introducing genes into the host cell, bacteria have only recently been investigated as possible triggers of cancer. The underlying mechanisms are less clear. "Now the teams around Dr. Sigal and Prof. Meyer, in cooperation with other cooperation partners, overcome the dogma that had previously applied that bacterial infections would only affect cells on the surface, ”said the Charité.

Basis for the development of new treatment approaches?
"Helicobacter pylori causes a lifelong infection and increases the number of long-lived cells with stem cell potential in the gastric glands," explains Dr. The speed of stem cell division is increased, which ultimately leads to pathological changes in the epithelium. The current study provides a better insight into the mechanisms that can trigger gastric cancer and also provides "more general information on how chronic bacterial infections can disrupt tissue function and thus increase the risk of cancer", adds Prof. Meyer. In the long term, the current findings can also help advance the development of improved treatment approaches, the researchers hope. (fp)

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Video: Helicobacter pylori-induced Gastric Cancer: Tragic Triangulations (December 2021).