Research Why does Helicobacter pylori cause stomach cancer?

Mechanism of development of gastric cancer in Helicobacter infections

Bacteria of the genus Helicobacter pylori can cause gastric ulcers and even stomach cancer in humans. Scientists at the Friedrich-Alexander-University Erlangen-Nuremberg (FAU) have now deciphered the mechanisms by which the bacteria lead to the development of gastric cancer. This also opens hope for new therapeutic approaches.

Helicobacter pylori is considered the main cause of gastric cancer, which is one of the five deadliest cancers, killing around 750,000 patients annually, the FAU said, citing World Health Organization (WHO) figures. Now researchers have succeeded in decoding two mechanisms by which the bacterium leads to the development of gastric cancer. The current findings could also contribute to the development of new therapeutic approaches, according to the FAU. The results of the researchers were published in the journal "Cell host & microbe".

Scientists have deciphered the mechanism by which Helicobacter pylori infections lead to gastric cancer. (Image: fotoliaxrender / fotolia.com)

Helicobacter pylori represents a significant health risk

Infection with the bacterium Helicobacter pylori is known to be a significant risk factor for gastritis, gastric ulcer and stomach cancer. The increasing resistance to antibiotics also complicates the treatment of infections. The mechanisms of Helicobacter infections leading to gastric cancer have now been joined by an international team of researchers led by Drs. Nicole Tegtmeyer from the Department of Microbiology at 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 of stomach acid. The team around Dr. Tegtmeyer found that the H. pylori bacteria use a secreted enzyme, the protease HtrA, as a kind of 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 into the layer of epithelial cells," which allows bacteria to penetrate "deeper, normally germ-free tissue layers" and cause further damage, the researchers explain. This starts the development of stomach cancer.

Molecular injection of bacteria

However, this is not the only mechanism that the bactans trigger. The first step is followed by a much more dangerous, the scientists report. A needle-like process known as the type IV secretion system is subsequently activated and functions in a similar way to a "molecular syringe," the FAU reports. This injects, via a receptor-dependent mechanism, a bacterial toxin called CagA protein into the bottom of the host cells. In turn, the injected CagA will reprogramm the host cell to cause cancer.

Camouflaged bacteria

Last but not least, the CagA protein also affects the human immune system and the inflammation, "so that the bacteria are not recognized and therefore not eliminated," explain the experts. 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 "(new) important new approaches for anti-bacterial therapy, since HtrA and CagA are excellent as new drug targets." In addition, the group had already begun to test specific inhibitors of HtrA. Dr. Tegtmeyer and colleagues hope that such drugs can either completely prevent Helicobacter infection or prevent CagA injection. (Fp)