Nerve activity in the cerebral cortex can drive the growth of deadly brain tumors called high-grade gliomas, new research has found. The finding, from a study of mice with human brain tumors, provides a surprising example of an organ's function driving the growth of tumors within it, according to Michelle Monje, MD, PhD, the Stanford neuroscientist who led the work. The work appears online today in Cell.
High-grade gliomas include tumors that affect children, teens and adults. They are the most lethal of all brain tumors, and their survival rates have scarcely improved in 30 years. Monje's team and others around the world are trying to learn how the tumors arise and grow, with the hope that this understanding will enable development of new drugs that specifically attack the tumors' vulnerabilities.
From our press release about the research:
Monje's team identified a specific protein, called neuroligin-3, which is largely responsible for the increase in tumor growth associated with neuronal activity in the cerebral cortex. Neuroligin-3 had similar effects across the different types of high-grade gliomas, in spite of the fact that the four cancers have different molecular and genetic characteristics.
"To see a microenvironmental factor that affects all of these very distinct classes of high-grade gliomas was a big surprise," Monje said.
The identity of the factor was also unexpected. In healthy tissue, neuroligin-3 helps to direct the formation and activity of synapses, playing an important role in the brain's ability to remodel itself. The new study showed that a secreted form of neuroligin-3 promotes tumor growth.
"This group of tumors hijacks a basic mechanism of neuroplasticity," Monje said.
Blocking the tumor-stimulating effects of neuroligin-3 might be an effective treatment for high-grade gliomas, Monje added.
In the video above, Monje describes some of the earlier work that led her team to ask whether nerve activity could drive tumor growth. In the healthy brain, it's important for neuronal activity to be able to modify how the brain grows and develops, she explains - this is how experience changes our brains. But: "The growth-inducing effects of neuronal activity are very robust and it made me wonder if a similar physiology was being hijacked by glioma cells," she says in the video.
Previously: Emmy nod for film about Stanford brain tumor research -- and the little boy who made it possible, Big advance against a vicious pediatric brain tumor and New Stanford trial targets rare brain tumor