The idea centres on a cell-signalling system that relies on acetylcholine, previously thought to act only as a neurotransmitter in the brain and nerves. But the latest evidence suggests that it might double up as a growth factor outside the nervous system.
Eliot Spindel's team at the Oregon National Primate Research Center in Beaverton has been studying cells from patients with a type of lung cancer called small cell lung carcinoma. They discovered that some of the tumour cells possessed receptors for acetylcholine - and not only that, the fast-growing cells also made large amounts of acetylcholine.
This gave them the idea that the tumour cells were locked into a feedback loop in which the acetylcholine they made stimulated them to carry on growing and dividing. They tested this idea by investigating what would happen if they broke the loop. Sure enough, when they treated the tumour cells with atropine, which blocks acetylcholine receptors, the self-stimulating cells stopped growing.
Small cell lung carcinoma is closely linked to smoking. The main reason smoking causes cancer is because carcinogens in the smoke trigger pre-cancerous mutations in DNA. But smoking may also feed into the loop after these mutations have developed, because nicotine is known to be a strong activator of acetylcholine receptors. This means it could kick-start or accelerate the feedback loop in cancerous cells. "Our discovery reveals the little extra push by nicotine," says Spindel.
If acetylcholine boosts tumour growth, it might be possible to adapt drugs like atropine to treat lung cancer. But developing such drugs will not be easy. "You must find the right dose, or a pathway unique to lung cancer that doesn't affect the nervous system," Spindel says.
Nor is it yet clear if this feedback mechanism plays a role in other kinds of cancer. What is certain is that stopping smoking is still by far the best solution, says Spindel, whose findings appear in Life Sciences (vol 72, p 2159). "This loop can be revved up by smoking," he warns, "so there's no question that not smoking is the best thing you can do."
Marcus Munafo, who works for Cancer Research UK at the Institute of Health Sciences in Oxford, agrees. "But in the light of the new findings, it would be worth looking into whether or not stopping smoking makes a difference to survival rates in people already diagnosed with lung cancer," he says.
Written by Andy Coghlan
New Scientist issue: 29 March 2003
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