Gene Protects Against Tumors

A gene known as toll-like receptor 4 (TLR4) is part of the innate immune system, which forms the front line of defense against infection. To determine the role of TLR4 in inflammation, the researchers gave mice prone to lung cancer a preservative known to cause lung inflammation. Primary tumor formation also was measured in mice known to have cancer. Mice with both functional and altered TLR4 were used in all protocols. The results showed that mice that had TLR4 removed or altered had 60% more tumors than mice that had intact receptors, showing a protective role for the gene. The findings were reported in the December 7, 2005, issue of the "Journal of the [U.S.] National Cancer Institute.

"We can't attribute the number of tumors per mouse to TLR4 alone, but it accounts for a significant portion of it,” said Steven Kleeberger, Ph.D., chief, laboratory of respiratory biology at the U.S. National Institute of Environmental Health Sciences (NIEHS, Bethesda, MD, USA), which conducted the research. "TLR4 acts like the brake of a car,” he explained. "If you take the brake or receptor away, you see more increases in tumor development, more inflammation, and more mortality.”

Prior research has indicated an association between chronic lung inflammation and lung cancer but the mechanisms were not well understood. Chronic bronchitis and asthma, for example, are known to increase the risk of lung cancer. Inflammation has been implicated as a contributing factor to several human cancers.

"What we found is the innate immune system, particularly TLR4, plays a critical role in protecting against the development of tumors and chronic inflammation,” said lead author Alison Bauer, Ph.D. "It suggests that targeting the innate immune system may be a useful tool in fighting a variety of human diseases, including cancer.”





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