Suspicious hybrids. Gastric tumor cells that have both a bone-marrow-derived cell marker and a gastric epithelial cell marker (yellow label) are raising questions about the origins of stomach cancer.

Don't Trust the Help

A surprising new study has researchers rethinking the origins of gastric tumors.

Stomach cancer is a major cause of cancer deaths, especially in developing countries. About 15 years ago, researchers linked stomach cancer to infection with the ulcer-causing bacterium Helicobacter pylori. H. pylori infections apparently foster stomach cancer because of the persistent inflammation they produce. Most researchers thought that inflammatory cells probably spurred epithelial cells in the stomach lining to become cancerous. But in the 26 November issue of Science, researchers offer a more radical possibility--that the cells that ultimately give rise to cancer are not the epithelial cells but bone marrow stem cells that are recruited to try to repair the stomach lining.

To study the role of bone-marrow-derived cells in stomach cancer, a team led by JeanMarie Houghton of the University of Massachusetts Medical School in Worcester and Timothy Wang, who is now at Columbia College of Physicians and Surgeons in New York City, and their colleagues used a strain of mice that, when infected with H. felis, develop gastric changes similar to those seen in humans infected with H. pylori. Before infecting the mice, however, the researchers irradiated them to destroy their bone marrow; they then gave the rodents transplants of marrow cells bearing a genetically engineered marker that allows the cells to be distinguished from the animals' own cells.

After about 20 weeks of infection, the labeled bone marrow cells began incorporating into the stomach lining. There they started to differentiate. But the resulting cells weren't completely normal. Their shapes were distorted and they showed enhanced growth abnormalities similar to those of cells undergoing early cancerous transformation. Eventually, they produced cancerous tumors.

The results further support the idea that persistent inflammation fosters cancer development. Perhaps more intriguing, Houghton and Wang's results lend credence to the controversial new notion that cancer may arise from stem cells (Science, 5 September 2003, p. 1308 ), although some stem cell experts say they aren't convinced that the bone marrow cells are behaving as proposed by the UMass, Worcester, team. They note that the researchers haven't definitively ruled out the possibility that the bone marrow cells fused with stomach epithelial cells.

Still, the paper will likely spark a great deal of research interest."What this has done is open up a new field in gastric carcinogenesis," says Helicobacter expert Richard Peek of Vanderbilt University School of Medicine in Nashville, Tennessee."It's really quite a novel concept," says Emad El-Omar, a Helicobacter researcher at the University of Aberdeen, U.K."It will set people to thinking quite hard" about the origins of stomach cancer, he says.

Related sites
Houghton and colleagues' Science paper
More about H. pylori from the U.S. Centers for Disease Control and Prevention