Cancer And Infections: Are There Common Mechanisms?
Researchers in Italy have demonstrated how Helicobacter pylori triggers the first step of cancer development in cells of the gastric mucosa. Scientists of the German Cancer Research Center are investigating a key molecule in the development of cancer, infection and inflammation.
Once again, there is evidence about cell polarity and cancer. If you remember, in the past I talked about visualizing cells knowing their top and bottom.
The bacterium Helicobacter pylori is responsible for the development of stomach ulcers and also of stomach cancer. Helicobacter is equipped with special enzymes that enable it to survive the acid attacks by the stomach. Like a number of other bacterial pathogens, Helicobacter injects a protein into the epithelial cells of the gastric mucosa. While this injection is used by other pathogens to get access into the cell, Helicobacter's protein, called CagA, causes a whole range of dramatic changes in the cell biology.
Like all epithelial cells, those of the gastric mucosa have two sides with different functions: One faces outward, into the organ lumen, the other is in contact with the blood supply of the tissue. Between the two poles, the cell walls form a tight barrier via close contacts. Helicobacter dramatically disrupts this order. Following CagA injection, epithelial cells lose their polarity, the contact sites break apart. The cells form tiny foot-like extensions that make them mobile and start breaking through the basal membrane that separates them from the blood vessels. CagA causes similar changes in a cell like some cancer genes do. It is presumed in this study that CagA thus triggers the first step in the development of gastric cancer.
Assistant Professor Dr. Jan Mollenhauer, Division of Molecular Genome Analysis at the DKFZ, believes that a molecule called DMBT1 plays a key role in cancer development, infection and inflammation. The gene coding for DMBT1 first attracted attention by its absence: Mollenhauer discovered that the genetic information for DMBT 1 is missing in cells of malignant brain tumors. Meanwhile it is known that the DMBT1 gene is completely or partly lost in 84 percent of tumors that originate from epithelial cells. Numerous results also indicate that DMBT1 plays a role in infection defense. Thus, the protein binds and clots viruses and bacteria, which presumably causes them to lose their infectiousness. In addition, DMBT1 attracts immune cells to the infection site.
Mollenhauer's recent results show that DMBT1 is also involved in inflammatory processes. He reports that cells of the intestinal mucosa increase their DMBT1 production as a response to inflammatory stimuli. In cells of the inflamed intestinal mucosa of patients with Crohn's disease, NOD2, a protein that is a key sensor of the cell for bacterial infections, gives the signal for a strong increase of DMBT1 production.
The study presumes that complex diseases such as cancer, infection and inflammation, have common underlying molecular mechanisms.