New Clues to Cause of Stomach Cancer

Researchers have found that mutations on a receptor molecule called gp130 in mice resulted in symptoms that mirrored those of gastric cancer and large bowel inflammation in humans, suggesting targets for drugs to treat these conditions. The research was reported in the October 2002 issue of Nature Medicine.

The gp130 molecule is found on the surface of cells and is traditionally involved in helping to regulate the body's immune system. The molecule serves as a molecular antenna, transmitting instructions from cytokines to individual cells, telling them how to respond to their environment. The researchers were surprised when mice carrying the mutations in gp130 developed cellular changes similar to those of gastric cancer.

"Nobody suspected that interference with the messenger service engaged by gp130 could be linked with a 100% prevalence of early stages of gastric cancer in mice,” said Andy Giraud, associate professor at the University of Melbourne (Australia) and a member of the research team.

On set of mice had a single amino acid change to the gp130 molecule, which induced the changes reminiscent of early gastric cancer. A second set of mice has a small chunk chopped off the end of the molecule. This set showed reduced ability to repair damage in the colon and rectum, making them susceptible to intestinal injury resulting in large bowel inflammation.

"What has been designed as a regenerative mechanism gets out of control in the stomach with one mutation, while not being activated in the large bowel as a result of the other mutation. What we have yet to find is the cancer spreading to other organs, which is what eventually kills patients,” said Dr. Matthias Ernst, of the Ludwig Institute for Cancer Research in Melbourne, also a member of the research team.




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