A team of scientists working at the Max Planck Institute in Berlin in collaboration with researchers in Stanford, California, have uncovered a possible mechanism for bacteria’s ability to cause gastric carcinoma, one of the leading causes of cancer-related deaths.
The bacterium Helicobacter pylori chronically infects around half of all humans, but its ability to cause cancer has been a source of confusion for scientists. While it is known that viruses cause cancer by inserting oncogenes into host cell DNA, bacteria do not deposit transforming genes into their host cells.
Thomas F. Meyer and his colleagues at the Max Planck Institute have spent many years investigating H. pylori and the changes it induces in the stomach epithelium. Curious as to how malignancy could be induced in an environment with such rapidly replaced cells, they theorized that the answer may lie in the stem cells found at the the bottom of the glands of the stomach as these are the only long-lived cells in the stomach. A discovery by Michael Sigal, a clinical scientist of the Charité - Universitätsmedizin Berlin who joined the team, found that H. pylori not only infects the surface cells, but that some of the bacteria manage to invade deep into the glands and reach the stem cell compartment. The researchers were able to confirm that these stem cells respond to infection by increasing their division, thus producing more cells.
Experiments in mice revealed that stomach glands contain two distinct stem cell populations. Both respond to the signaling molecule Wnt, but in myofibroblast cells in the connective tissue layer the glands produce a second stem cell driver signal called R-spondin that the two stem cell populations respond to differently. Following infection by H. pylori, R-spondin is ramped up causing more slowly cycling stem cell populations to be silenced and increasing the activity of the faster cycling stem cell population.
"Since H. pylori causes life-long infections, the constant increase in stem cell divisions may be enough to explain the increased risk of carcinogenesis observed", said Meyer. The authors believe these findings may also help explain the mechanism behind other types of bacterially induced cancer.
Image: Cross section of stomach glands, showing the outline of individual cells in green and their nuclei in blue. Image courtesy of MPI for Infection Biology in Berlin.