A pre-cancerous tissue may cope better with persistent bacterial infections

Thomas F. Meyer wins a 2.5M EUR grant from the European Research Council (ERC)

April 17, 2020

Thomas F. Meyer, Director at the Max Planck Institute for Infection Biology, receives an Advanced Grant for his project "Metaplasia as an adaptive response to chronic microbial infections" on the role of bacterial infections in the development of human cancer. Following his successful research at Max Planck, he will carry out the project after his emeritation in August 2020 as Senior Professor at Charité - Universitätsmedizin Berlin.

The epithelium covers the internal surfaces of our organs, including various mucosal tissues. The mucosa is where microbes colonize our bodies and whereby contact with toxic agents may occur. Sometimes, such encounters can be quite harsh if pathogens come into play, and it is, thus, not surprising that most cancers originate here. Several chronic bacterial infections have been implicated in the formation of human cancers, with Helicobacter pylori representing a well-known paradigm of a cancer-inducing bacterium. While the precise mechanisms by which bacteria can cause cancer are not well understood, it is vital to monitor these etiological processes in order to devise protective measures against this devastating disease.

Under this notion, Prof. Thomas F. Meyer and his team aim to step in and explore the origin of microbe-induced epithelial cancer. They will start off from a very curious observation made by clinicians and pathologists – during the life-long colonization of the stomach mucosa by the bacterium H. pylori, the inflamed gastric tissue tends to convert into a novel type of epithelial tissue that mimics the intestine. This process is called intestinal metaplasia and constitutes a starting point of gastric cancer development. Intriguingly though, once intestinal metaplasia emerges, H. pylori disappear from these metaplastic mucosal sites, occasionally leading to complete elimination of these bacteria from the stomach. On the one hand, this implies that cancer progression may proceed under pathogen-free conditions. On the other hand, the development of gastric intestinal metaplasia may be viewed as an efficient antimicrobial defense. Thus, Prof. Meyer proposed that “the gastric mucosa may adapt towards a different type of mucosa at the cost of a slightly increased risk of cancer in order to get rid of this potentially dangerous bacterial pathogen. The immediate danger of H. pylori infections is, namely, ulcer formation, the destruction of gastric tissues that may lead to intense bleeding and even rupture of the stomach, a deadly condition if untreated.”

Accordingly, escape from an instant life-threatening condition may, in the long term, predispose to cancer. To investigate this provocative hypothesis, Meyer’s team plans to examine the modifications in the gastric human epithelium that take place in response to H. pylori infection and during the development of intestinal metaplasia. In this regard, an interesting observation has already been made. The researchers demonstrate that a distinct cancer-provoking mutation, often seen in the stomach in the course of H. pylori infection and the development of intestinal metaplasia, empowers the epithelium to produce effective antimicrobial factors. This observation constitutes the clue to Meyer’s work program by which they aim to unravel the molecular links between (i) the genomic mutations and epigenetic changes that pathogens induce in the epithelium during chronic infections, (ii) the antimicrobial and tissue-protective effects that are elicited through such genomic alterations, and (iii) the associated increase of risk that results in cancer.

If successful, this challenging project will not only establish a paradigm shift on our understanding of the emergence of certain human epithelial cancers, but it will also highlight an entirely new level of immune defense alongside the well-studied branches of innate and adaptive immunity. Ultimately, by helping to reveal the causality of human cancers, this research will insinuate new ways of cancer prevention.

Thomas F. Meyer is director of the department of molecular biology at the Max Planck Institute for Infection Biology. He is a science leader in the field of host-pathogen interactions and a member of EMBO and the German Academy of Sciences Leopoldina. The focus of research has made a transition recently into the role of bacterial infections in cancer. The prestigious 5-year-long advanced ERC grants, awarded to established investigators, have a success rate of ~10%. It is the first time that an awardee from the Max Planck Institute for Infection Biology receives this grant. Despite his upcoming retirement from the institute later this year, the research will be continued in the Charité University of Medicine, where a new laboratory is founded.

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