The most common type of brain tumor in children, pilocytic astrocytoma (PA), accounts for about 15% of all pediatric brain tumors. Although this type of tumor is usually not life-threatening, the unchecked growth of tumor cells can disrupt normal brain development and function. Current treatments focus mainly on removing the tumor cells, but recent studies have shown that non-cancerous cells, such as nerve cells, also play a role in brain tumor formation and growth, suggesting novel approaches to treating these cancers.
Scientists have long known that a nerve cell signaling chemical called glutamate can increase growth of cancers throughout the body, but despite years of investigation, they haven’t figured out exactly how this happens or how to stop it. Now, an interdisciplinary team of researchers at Washington University School of Medicine in St. Louis has uncovered how glutamate regulates pediatric brain tumor growth. Using tumor cells isolated from patient PA samples, they found that PA cells hijack the function of proteins on cells’ surface that normally respond to glutamate, called glutamate receptors. Instead of transmitting glutamate’s typical electrical signal, these receptors are reprogrammed to send signals to increase cell growth.
They also observed that drugs that block these glutamate receptors — including memantine, which is approved to treat dementia and Alzheimer’s disease — reduced human pediatric brain tumor growth in mice, a finding that points to a potential new treatment opportunity.
The results appear Sept. 1 in Neuron.
“With these kinds of pediatric brain tumors, we just don’t have that many tools in our toolbox for treating patients,” said senior author David Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology at WashU Medicine. Gutmann treats patients at Siteman Kids at St. Louis Children’s Hospital. “The potential to repurpose drugs that are already in use for other neurological disorders means we may have another trick up our sleeves for treating patients.”
The research team, which included first author Corina Anastasaki, PhD, a research assistant professor of neurology at WashU Medicine, also showed for the first time that glutamate receptors abnormally couple with growth receptors in PAs to fuel the tumors. The findings offer a roadmap for future studies to explore if the same process is happening in different types of cancers.