Hindering glutamate slows rat brain cancer.Drugs that thwart the effect of a chemical secreted by certain cancerous brain cells could slow the growth of deadly brain tumors, a new study suggests.
The chemical, an amino acid amino acid (əmē`nō), any one of a class of simple organic compounds containing carbon, hydrogen, oxygen, nitrogen, and in certain cases sulfur. These compounds are the building blocks of proteins. called glutamate glutamate /glu·ta·mate/ (gloo´tah-mat) a salt of glutamic acid; in biochemistry, the term is often used interchangeably with glutamic acid.
1. A salt of glutamic acid. , normally acts as a neurotransmitter that brain cells use to signal each other. To serve this purpose, glutamate must move cleanly between cells. However, excess glutamate spilled into the space between cells can cause neurons, the information-carrying brain cells, to fire out of control and die.
In a healthy person, any excess glutamate is promptly gobbled up by glial cells, which are brain cells that support neurons. But in many glial-cell cancers, or gliomas, the tumor cells instead secrete glutamate. The resulting abundance of the neurotransmitter appears to kill neurons and create room for the cancerous glial cells to grow in the limited space within the skull. Moreover, glutamate secreted by glioma glioma /gli·o·ma/ (gli-o´mah) a tumor composed of neuroglia in any of its states of development; sometimes extended to include all intrinsic neoplasms of the brain and spinal cord, as astrocytomas, ependymomas, etc. cells may cause surviving neurons to misfire and initiate epileptic seizures.
Scientists in Europe reported earlier this year that glutamate enhances the growth of various cancerous cell lines in lab dishes, whereas glutamate blockers thwart such growth. Wojciech Rzeski of Humboldt University in Berlin and his colleagues reported these findings in the May 22 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. .
In the September NATURE MEDICINE, New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of scientists now report that two compounds that impede excess glutamate's effect on neurons can salvage some of these cells in rats. In so doing, the drugs inhibit glioma's spread.
The researchers examined brains of rats with gliomas that naturally did or didn't secrete excess glutamate. Tumors releasing abundant glutamate were significantly larger than the rest, says study coauthor Takahiro Takano, a neuroscientist at New York Medical College New York Medical College is a center for graduate medical education located in Westchester County, a suburb half an hour north of New York City. This private university comprises the School of Medicine, which grants the M.D. in Valhalla.
Takano and his colleagues also found that two chemicals--dubbed MK801 and memantine--slow the growth of some glioma cells in lab dishes. When the researchers injected the compounds into rats with glutamate-releasing gliomas, both slowed tumor growth.
The study "provides compelling evidence that [glutamate] gives the tumor cells a growth advantage," says Harald Sontheimer, a neurobiologist neurobiologist
a specialist in neurobiology. at the University of Alabama The University of Alabama (also known as Alabama, UA or colloquially as 'Bama) is a public coeducational university located in Tuscaloosa, Alabama, USA. Founded in 1831, UA is the flagship campus of the University of Alabama System. in Birmingham.
How some tumor cells produce excess glutamate is unclear, Takano says. In healthy people, glial cells draw small amounts of glutamate from the blood and pass it to neurons for its controlled use as a neurotransmitter.
Besides destroying neurons, glioma cells engender inflammation. This attracts the brain's housekeeping cells, which haul away remains of the dead neurons, Takano says. Inflammation may also spur angiogenesis--the process of building new blood vessels--which nourishes a growing tumor, he says.
MK801 and memantine work by binding to receptor molecules on the surface of neurons. This leaves fewer docking sites for glutamate, which prevents it from overstimulating the cells, Sontheimer says. With no place to grow and little angiogenesis angiogenesis /an·gio·gen·e·sis/ (-jen´e-sis) vasculogenesis; development of blood vessels either in the embryo or in the form of neovascularization or revascularization.
n. , the tumor is stifled.
However, occupying a receptor on neurons can keep them from firing normally and thus may disrupt brain function. Memantine seems to block receptors enough to ward off excess glutamate but still permits neurons to function, Takano says. Already prescribed in Europe for some brain disorders, it shows few side effects. But MK801 occupies more glutamate receptors, preventing the neurons from firing, and would be too strong for use in people, Takano suggests.
These and other recent studies "open up an entirely new treatment approach to fatal central nervous system tumors," Jeffrey D. Rothstein and Henry Brem of Johns Hopkins University Johns Hopkins University, mainly at Baltimore, Md. Johns Hopkins in 1867 had a group of his associates incorporated as the trustees of a university and a hospital, endowing each with $3.5 million. Daniel C. Medical Institutions in Baltimore say in the September NATURE MEDICINE.