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Stomach Cancer May Start in Bone Marrow

Mouse study questions long-held belief about disease origins

FRIDAY, Nov. 26, 2004 (HealthDayNews) -- Stomach cancer may originate from bone marrow cells rather than stomach cells, as was previously believed.

A new study in mice found that stomach cancer cells began as bone marrow cells that had migrated to the stomach. The bone marrow cells traveled to the stomach in response to inflammation caused by an infection with the bacterium that causes ulcers, Helicobacter pylori.

These findings, published in the Nov. 26 issue of Science, are in stark contrast to the commonly held belief that cancers originate from the tissue in the surrounding area, meaning that it was believed that stomach cancer begins from stomach stem cells.

"In the last five years or so, we've learned that bone marrow-derived stem cells can go to sites of injury and mimic epithelial cells [from that region], which raised the possibility that bone marrow cells could play a role in the development of cancer in that area," said one of the study's authors, Dr. Timothy Wang, chief of the division of digestive and liver diseases at Columbia University College of Physicians and Surgeons in New York. Most of the study was done while Wang was working at the University of Massachusetts Medical School.

"This study was designed to ask the question: Which is the cell of origin for stomach cancer?" Wang added.

To answer that question, Wang and his colleagues used a mouse model of the H. pylori infection and combined it with bone marrow transplants. First, the mice underwent almost lethal irradiation to destroy their natural bone marrow.

The researchers then transplanted bone marrow that contained markers that could later be identified in other cells. Some of the markers were different colors, and one was a gender mismatch -- male cells were transplanted into females.

Before the mice were infected with the ulcer bug, the researchers looked for evidence of bone marrow cells in the stomach and found very few.

Next, the researchers infected the mice with an H. pylori-like bacterium. After 14 weeks, there were still "no signs of bone marrow coming in," according to Wang.

But when the researchers followed-up between 20 and 52 weeks, which more closely follows the type of chronic infection and inflammation that might be present in human cases, they found that bone marrow cells were present in the stomach, apparently in an attempt to repair the damage caused by the bacteria.

Wang said that the bone marrow cells came in to replace the damaged cells, but then became damaged themselves and eventually turned into stomach cancer, a disease that affects 24,000 Americans every year, according to the National Cancer Institute.

Wang said he believes the results will be similar in humans, but added that it would be difficult to do this type of study in people because there is no easy way to insert markers into the bone marrow cells.

He said these findings "may offer a number of different opportunities. By defining the cancer stem cells, we may be better able to understand the cancer and how it progresses." He said this could lead to better ways to diagnose and treat stomach cancer, and possibly other cancers that are caused by inflammation.

Dr. Roshini Rajapaksa, a gastroenterologist at New York University Medical Center, said this study "definitely gives us a new way of looking at how cancer forms."

She agreed that this research could eventually lead to new treatments and new ways of diagnosing the disease, which is welcome news for a disease with no "great treatments right now."

In the meantime, however, she added it's important for people to realize that not everyone with H. pylori, a relatively common infection, will go on to develop stomach cancer.

More information

To learn more about stomach cancer, visit the National Cancer Institute.

SOURCES: Timothy Wang, M.D., professor of medicine, and chief of digestive and liver diseases, Columbia University College of Physicians and Surgeons, New York City; Roshini Rajapaksa, M.D., gastroenterologist, New York University Medical Center, and clinical instructor, New York University School of Medicine, New York City; Nov. 26, 2004, Science
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