Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, which chronically infects around half of all humans. However, unlike tumor viruses, bacteria do not deposit transforming genes in their host cells and how they are able to cause cancer has so far remained a mystery.
An interdisciplinary research team has now discovered that the bacterium sends stem cell renewal in the stomach into overdrive - and stem cell turnover has been suspected by many scientists to play a role in the development of cancer. By showing that the stomach contains two different stem cell types, which respond differently to the same driver signal, they have uncovered a new mechanism of tissue plasticity. It allows tuning tissue renewal in response to bacterial infection.
While it is now clear that most cases of stomach cancer are linked to chronic infections with H. pylori, the mechanism remains unknown.
Crucially, they discovered that myofibroblast cells in the connective tissue layer directly underneath the glands produce a second stem cell driver signal, R-spondin, to which the two stem cell populations responded differently. It is this signal, which turned out to control the response to H. pylori: Following infection, the signal is ramped up, silencing the more slowly cycling stem cell population and putting the faster cycling stem cell population into overdrive.