Mechanism of gastric cancer development in Helicobacter infections
Bacteria of the genus Helicobacter pylori can cause stomach ulcers and even stomach cancer in humans. Scientists at the Friedrich Alexander University in Erlangen-Nuremberg (FAU) have now deciphered the mechanisms by which the bacteria lead to the development of stomach cancer. This also opens up hope for new therapeutic approaches.
Helicobacter pylori are considered the main cause of gastric cancer, which is one of the five most deadly cancers and about 750,000 patients die of the disease annually, the FAU reports, citing the figures from the World Health Organization (WHO). The researchers have now succeeded in deciphering two mechanisms by which the bacterium leads to the development of stomach cancer. The current findings could also contribute to the development of new therapeutic approaches, according to the FAU communication. The researchers' results were published in the specialist magazine "Cell host & microbe".
Helicobacter pylori has a significant health risk
Infection with the bacterium Helicobacter pylori is known to be a significant risk factor for inflammation of the stomach, gastric ulcers and stomach cancer. The increasing resistance to antibiotics also makes the treatment of infections more difficult. The mechanisms by which Helicobacter infections lead to stomach cancer have now been researched by an international team of researchers led by Dr. Nicole Tegtmeyer from the Chair of Microbiology at the FAU.
Bacteria break through the protective layer of the gastric mucosa
The scientists observed how the bacteria destroy the protective layer in the stomach, which consists of closely spaced epithelial cells that protect the stomach from attacks by gastric acid. The team around Dr. Tegtmeyer found that the H. pylori bacteria use a secreted enzyme, the protease HtrA, as a weapon to break through the protective layer of the gastric mucosa, reports the FAU. “HtrA cuts three proteins (occludin, claudin-8 and e-cadherin) and creates a breakthrough in the layer of epithelial cells”, via which the bacteria can penetrate into “deeper, normally germ-free tissue layers” and cause further damage, the researchers explain. This starts the development of stomach cancer.
Molecular injection of the bacteria
However, this is not the only mechanism that the bacteria activate. The first step is followed by an even more dangerous one, the scientists report. A needle-like extension, which is referred to as a type IV secretion system, is then activated and functions like a “molecular syringe”, reports the FAU. This injects a bacterial toxin, the so-called CagA protein, on the underside of the host cells via a receptor-dependent mechanism. The host cell is in turn reprogrammed by the introduced CagA so that cancer can develop.
Last but not least, the CagA protein also influences the human immune system and inflammation, "so that the bacteria are not recognized and therefore not eliminated," the experts explain. This is a crucial way for the long-term survival of Helicobacter pylori bacteria in the human stomach.
Starting points for new therapies
According to the scientists, the current findings show "important new starting points for an anti-bacterial therapy (because), HtrA and CagA are excellent as new drug targets." In addition, the working group has already started to test specific inhibitors against HtrA. Dr. Tegtmeyer and colleagues hope that the corresponding active ingredients can either completely prevent Helicobacter infection or prevent the CagA injection. (fp)