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Wake Forest Scientists Develop Colony of Mice That Fight Off Virulent Cancer

WINSTON-SALEM, N.C. – Scientists at the Comprehensive Cancer Center of Wake Forest University have developed a colony of mice that successfully fight off virulent transplanted cancers.

"The mice are healthy, cancer-free and have a normal life span," the 10-member team reported in the Proceedings of the National Academy of Sciences online edition to be published the week of April 28.

The transplantation of the cancer cells in these special mice provokes a massive infiltration of white blood cells that destroy the cancer, said Zheng Cui, M.D., Ph.D., associate professor of pathology at Wake Forest University Baptist Medical Center and the lead scientist

"The destruction of cancer cells by these leukocytes is rapid and specific without apparent damage to normal cells," Cui said. "These observations suggest a previously unrecognized mechanism by which the body can fight off cancer."

The discovery of a genetic protection from cancer in mice "may have potential for better therapy or prevention of cancer in people," the team said. It also could help explain why some people are protected against cancer despite prolonged and intense exposure to carcinogens..

The discovery also could help solve another mystery. For years, scientists have been searching for the mechanism that permits spontaneous regression of human cancers without treatment. Cui said these cases are well-documented, but occur rarely. The new mouse colony gives the team the opportunity to study the mechanism in an animal model.

Cui and his colleagues began the mouse colony almost by serendipity. As part of ongoing cancer studies, they were injecting a virulent type of cancer cell that forms highly aggressive cancers in all strains of laboratory mice and rats. When injected into the abdomen, the tumor grows exponentially, causing the abdomen to fill with fluid within two weeks. The cancer can then progress by metastasizing into the liver, kidney, pancreas, lung, stomach and intestine. But, said Cui, one male mouse unexpectedly remained free of the cancer despite repeated injections. The Wake Forest team was able to show this was genetic and to develop a colony from that single mouse. The colony, now about 700 mice, remains exclusively at Wake Forest. Meantime, the original mouse "remained healthy, cancer-free and eventually died of old age after a normal lifespan."

When the cancer-resistant mice were bred with normal partners, the researchers found that about half of their offspring were resistant to cancer cells, indicating that this genetic protection is dominant and is likely due to a change in one gene. The resistance continued in future generations.

Depending on the age of the mouse, some had complete resistance -- the cancer never got started -- while others displayed spontaneous regression -- the cancer started developing over a period of a couple of weeks, but then it rapidly disappeared in less than 24 hours.

"The mice became healthy and immediately resumed normal activities including mating," Cui said. They tested them again with another injection of the cancer cells. He said that once the mice developed the protection, they never again developed the cancer.

The researchers said the mouse model "represents a unique opportunity to examine cancer/host interactions."

Cui said the new mouse model also may help in solving another medical mystery -- why cancer becomes more common when people age.

The usual explanation is that mutations accumulate in the body, leading to precancerous conditions that eventually become cancer.

But, he said, the mouse model suggests that the body''s natural protection -- which scientists call host resistance -- declines with age.

"This is at a preliminary stage, but very promising," said Mark Willingham, MD., professor of pathology and a collaborator. "Our hope is that, some day, this will have an impact on human cancer."

The ongoing research is supported by the Charlotte Geyer Foundation, the National Cancer Institute and, most recently, by the Cancer Research Institute.

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