Cleaning up glutamate slows deadly brain tumors

From New Orleans, at a meeting of the Society for Neuroscience

A protein that removes excessive amounts of the amino acid glutamate from around nerve cells may protect a brain from tumors, according to two studies. Researchers could soon test whether drugs that increase production of this glutamate-sweeping protein stop otherwise-fatal cases of brain cancer.

Glutamate is essential to the healthy brain. It’s one of the many compounds that nerve cells use to signal each other. Over the past few years, cancer researchers have discovered that many brain tumors, particularly ones called gliomas, secrete massive amounts of the amino acid. The tumors seem to wield glutamate as a machete of sorts, carving out room for growth by using the molecule to stimulate nerve cells until they die (SN: 9/1/01, p. 133: Available to subscribers at Hindering glutamate slows rat brain cancer).

The healthy brain uses the protein called excitatory amino acid transporter 2 (EAAT2) to mop us excess glutamate outside nerve cells. In previous studies, researchers at George Washington University in Washington, D.C., genetically engineered mice to overproduce EAAT2. The scientists recently injected glioma cells into the brains of these mutant mice and found that the resulting tumors grew more slowly than they would have in the brains of typical mice.

Moreover, the mutant mice were slower to start experiencing seizures caused by their brain tumors and suffered less nerve cell death around the tumors than normal mice do, says Jamie L. Maguire, now at the University of California, Los Angeles.

Kaleb H. Yohay of Johns Hopkins Medical Institutions in Baltimore recently surveyed the amount of EAAT2 in glioma samples from 60 patients. “There seems to be less of this major glutamate transporter in the higher-grade, more-invasive tumors,” he says. Having less EAAT2 may prolong the time that glutamate from a glioma can kill nerve cells, he suggests.

As part of an effort to identify new treatments for a wide range of brain diseases, Yohay’s colleague Jeffrey D. Rothstein recently screened more than 1,000 existing drugs, looking for ones that increase EAAT2 production. As it turned out, some common antibiotics do the trick. Given that there is no consistently effective treatment for gliomas, physicians will probably be eager to test such EAAT2 boosters on people with the tumors.

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