Stomach tissue from mice with stomach tumours, showing bone marrow-derived cells (in blue).
Study prompts rethink about what triggers a tumour
Stomach cancers may arise from stray bone-marrow cells rather than stomach cells, according to evidence in mice. The finding could overturn theories about the origins of cancer.
The study challenges a long-held assumption that stomach, lung and other cancers start when a cell within that tissue racks up mutations and starts to multiply uncontrollably.
Timothy Wang, currently at Columbia University in New York, and his colleagues wondered whether bone-marrow cells, which are thought to home in on infected and inflamed areas, might be sparking cancers. They studied mice infected with Helicobacter pylori, which is an ulcer-causing bacterium that triggers a large proportion of human stomach cancers.
The researchers wiped out the animals’ own bone marrow with radiation and then infused them with fresh bone-marrow cells. These were labelled with, for example, a glowing green protein, so that they could be tracked through the body.
Twenty weeks after the mice were infected with H. pylori, some of the bone-marrow cells had homed in on the stomach and divided, and tumours had formed. The study suggests that cancers are spawned by cells from the bone marrow rather than ones already resident in the stomach, and the researchers believe this may apply to humans too.
"It’s a very novel and astounding piece of work," says gastroenterologist Emad El-Omar at the University of Aberdeen, UK. "Everyone will reassess the way they talk about cancer," he predicts.
Inflamed tissue
Besides stomach cancers, the results suggest that bone-marrow cells may be the starting point for many other cancers linked to infection and inflammation. These include cancers of the oesophagus, lung, colon, cervix and liver, in which bone-marrow cells may also infiltrate the inflamed tissue.
Wang suggests that, during a long-term infection, cells that normally live in and repair the stomach lining are damaged or killed. Stem cells in the bone marrow move in to replace them, but they grow abnormally in the inflamed tissue, giving rise to cancers.
Before this study, researchers struggled to explain why a resident cell in the stomach might transform into a cancerous cell, El-Omar says. But it is easier to understand why a bone-marrow cell might do so.
Bone marrow contains an assortment of stem cells that are thought to divide and give rise to many tissue types in different situations. But it is not yet known what type of stem cell might be involved in triggering cancer.
Warning signals
The results might lead to new ways of diagnosing or treating stomach cancer, the second most common cause of cancer-related death in the world. For example, researchers might identify a protein in bone-marrow cells that is switched on when the cells are about to turn cancerous and use this to pick up imminent disease.
Alternatively, biologists might create drugs to block the bone-marrow cells from migrating to the inflamed area, suggests oncologist Richard Peek of Vanderbilt University in Nashville, Tennessee.
Experts say the study also raises a cautionary note for doctors who are using injections of bone-marrow stem cells as experimental therapy for treating heart disease and other conditions. Such an infusion might increase the risks of these cells lodging in the stomach or another inflamed area and triggering cancer. "No one knows what the risk is," Wang says.
References
1.Houghton J., et al. Science, 306. 1568 - 1571 (2004).
