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AN insidious type of brain tumour cuts a swathe through the brain by
secreting a compound that makes healthy neurons self-destruct. The discovery
could lead to treatments to combat this normally fatal disease.

Gliomas are among the deadliest of all cancers. In the US, most of the 20,000
people diagnosed annually die within 18 months. 鈥淚t鈥檚 a field people didn鈥檛
study too much because it was regarded as hopeless,鈥� says Maiken Nedergaard, a
cell biologist at New York Medical College in Valhalla.

To make room for themselves to grow, gliomas opt to destroy the healthy
tissue around them. But how do they do this? Recent research suggested that
gliomas secrete a neurotransmitter called glutamate. Although glutamate plays an
essential role in normal brain function, too much of it is dangerous. During
strokes, for example, excess glutamate overstimulates neurons and kills
them.

To find out if gliomas use glutamate in this way, Nedergaard and her team put
healthy neurons in a culture dish with one of two varieties of glioma
cells鈥攐ne called C6Glu+, which secretes high levels of glutamate, and
another that secretes much less. After 24 hours, only 14 per cent of the neurons
in the dish with C6Glu+ were still alive, compared with 86 per cent of neurons
in the other group. The C6Glu+ cells also formed fast-growing tumours when
injected into the brains of rats, while the cells that were poor at secreting
glutamate weren鈥檛 able to spread.

Nedergaard says this leads to a deadly cycle: the wreckage of dead neurons
killed by the tumours triggers an inflammatory response, which increases blood
flow to the area and brings nutrients to feed the growing tumour. 鈥淚t鈥檚 clever,
but also very scary,鈥� she says.

But the team also found that two commonly available drugs that block
glutamate will slow down the growth of gliomas. The drugs shrank tumours by up
to half when given to the rats a few days after the glioma cells were injected
into the brain.

鈥淭his suggests a different approach to [treating] tumours,鈥� says Jeffrey
Rothstein, a neurologist at Johns Hopkins University in Baltimore. Blocking
glutamate may turn out to be a more effective weapon against gliomas than
chemotherapy and radiation treatment, he says. Even better, the drugs are
already available. 鈥淔or years major pharmaceutical companies have been
developing anti-glutamate drugs for use in other disorders,鈥� Rothstein says.

Although many of these drugs were shelved because of nasty side effects,
Nedergaard says it might be possible to avoid these problems with smaller doses.
This should still work, she says, because the amount of glutamate gliomas
secrete is far less than the whopping increase associated with strokes.