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5-Animals: Lucky discovery uncovers cancer-proof mouse

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TITLE:  Lucky discovery uncovers cancer-proof mouse
SOURCE: The New Scientist, UK, by Shaoni Bhattacharya
DATE:   Apr 28, 2003

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Lucky discovery uncovers cancer-proof mouse

A cancer-proof mouse, which can survive being injected with any number of
cancer cells, has been discovered by US scientists. The discovery of the
resistant mouse could pave the way for future gene or drug therapies if
the mechanism by which it fights cancer can be understood

Researchers at the Wake Forest University School of Medicine in North
Carolina have now bred a colony of 700 cancer-proof mice from the
resistant male they stumbled across while doing other experiments.

Doctors have known for many years that in rare cases, cancers can
mysteriously clear up of their own accord. But this is the first time
such cancer-killing ability has been shown to be genetic.

"The power of this resistance seems to be unlimited," said biochemist
Zheng Cui, the study leader. "You can give them many, many tumour cells
and the mice get rid of them."

"This is at a preliminary stage, but very promising," adds pathologist
Mark Willingham, another member of the team. "Our hope is that, some day,
this will have an impact on human cancer."

 Seven generations

The scientists discovered the original cancer-proof mouse by luck during
experiments in which mice were injected with soft tissue cancers, called
sarcomas. Despite repeated injections, one mouse did not develop cancer.

When this mouse bred with a normal mouse, some of their offspring were
resistant. And these resistant mice were also able to confer resistance,
for at least seven generations. "The resistance appears to be caused by
just one gene, or a cluster of closely related genes," Cui told New Scientist.

The cancer-killing ability of the mice was unusually consistent with
different types of cancer. "What's surprising is it appears these mice
are able to recognise something in common to all cancer cell lines," said
Cui. "Usually it's difficult to find a common theme."

Willingham told New Scientist that the cancer cells are killed by the
mice in a "somewhat novel" way. The body's usual first line of defence
against invaders - white blood cells called T-cells - were not employed.
Instead the body's innate immune system, consisting of cells like
neutrophils and macrophages, attacked the tumour cells and ruptured them.

Previous mice bred so that their immune systems could beat cancer went on
the develop autoimmune diseases, but that did not happen with these mice.

One significant puzzle that remains is how the mice detect the cancer
cells in the first place. Cui speculates that some kind of diffusible
factor from the tumour may betray the deadly cells.

Paul Ko Ferrigno, a cancer biologist at the MRC's cancer cell research
unit in Cambridge, UK, calls the findings "very tantalising". "I'm
intrigued and excited. If they can pin down what the immune basis for
resistance to cancer is it should be straightforward to train a patient's
immune system to do the same," he told New Scientist. Although they are
preliminary, the study's findings have "huge potential", he says.

The top priority now, says Willingham, is to identify the mouse gene
responsible for the resistance. "Because of the Human Genome Project, we
could then look for a correlate gene in humans," he said.

Journal reference: Proceedings of the National Academy of Sciences: (doi/