New thinking on the source of gastric cancer

November 25, 2004

WORCESTER, Mass.-In a study published in the November 26 issue of the journal Science that provides a radically different view of the origins of gastric cancers, researchers at the University of Massachusetts Medical School identified a clear and unexpected link between stomach cancer and bone marrow-derived cells. JeanMarie Houghton, MD, PhD, an assistant professor in medicine and cancer biology at UMMS, and colleagues discovered that infection with Helicobacter felis (a bacterium related to Helicobacter plyori, which has long been understood to cause chronic inflammation and cancer in the lining of the stomach) leads to a vast influx of bone marrow-derived stem cells as the body tries to repair the damage caused by the bacterial infection. Houghton and colleagues showed that this flood of bone marrow-derived stem cells (BMDCs) can actually spark stomach cancer tumors.

Previous studies of H. pylori inflammation and gastric cancers have focused on damaged epithelial cells that line the stomach as the source of tumors. Houghton and colleague Timothy C. Wang, MD, formerly of UMMS and now at Columbia University Medical Center, showed that in mouse models it is the BMDCs themselves that form cancers, an unexpected development that may cause a shift in thinking about the formation and progression of such cancers.

"We have known for years that chronic inflammation causes cancer, yet we did not know precisely how," said Dr. Houghton. "Tissue stem cells, which are long-lived cells within organs that act to repair and replenish cells, have long been thought of as targets for carcinogens and the source of cancer. We show that bone marrow-derived stem cells participate in normal repair but, under conditions of inflammation, are unable to behave normally and instead progress towards cancer. This dramatically changes the way we think about cancer. If this model applies to human cancer, we will need to revise our approaches to prevention and treatment."

BMDCs have the ability to develop into any tissue type, but to do so they require the right environment and the right signals. In the infected stomach, the environment is damaged; there, BMDCs mutate and begin to progress toward cancer. The BMDCs' other properties-the capacity for unlimited growth, an ability to avoid apoptosis (cell death) signals, low requirements for growth factors, an ability to form supportive blood vessels-give them a significant growth advantage, making them difficult to control once mutated.

Gastric cancers kill approximately 12,000 people in the US each year. However, in developing countries where H. pylori infection is more common, the toll is far greater-nearly 600,000 worldwide. The source of infection itself is often hard to pinpoint but is often associated with lower socio-economic status and crowded conditions.
Houghton's work is expected to spur further research into other epithelial-based cancers, such as breast, pancreatic, and colon cancers.


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