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. 
 
 Using light stimulation 
 
 To conduct the study, Monje’s team employed optogenetics, a Stanford-developed technique that uses genetic manipulation to insert light-sensitive proteins into specific neurons, allowing the neurons to be activated with the flip of a light switch. Into the cerebral cortex of mice with these light-sensitive proteins, the team implanted cancer cells from a human pediatric cortical glioblastoma. After the tumors became established, neurons near the tumors were activated with light. The team then compared tumor growth between these mice and a control group with implanted tumors but without the nerve activation. Increased tumor proliferation and growth in the mice that received neurostimulation via optogenetics were the first indications that neuronal activity fed the brain tumors. 
 
 We’ve shown that brain function is driving these brain cancers. 
 
 The team performed follow-up experiments on slices of mouse brain to identify secreted factors that made the tumor cells proliferate. They then conducted biochemical analyses to identify neuroligin-3, confirm that the protein could stimulate tumor growth in cultured samples of several kinds of human high-grade gliomas and study which signals the protein uses within glioma cells to promote their growth. 
 
 In addition, the researchers examined neuroligin-3 data from the Cancer Genome Atlas, a large public database of human cancer genetics. More activity of the neuroligin-3 gene in high-grade gliomas was linked to shorter survival among patients with these tumors. 
 
 The study’s findings may open doors to new high-grade glioma treatments. Although, in theory, the results indicate that sedating patients to reduce neural activity could reduce brain tumor growth, this is unlikely to be accepted as an ethical or practical cancer therapy. A better approach, Monje said, would be to develop drugs that specifically block the tumor-stimulating activities of neuroligin-3, such as a drug that stops the protein from being secreted into the area around the cancer cells. 
 
 The lead authors of the study are graduate student Humsa Venkatesh, MD/PhD student Tessa Johung and postdoctoral scholar Viola Caretti, MD, PhD. 
 
 Other Stanford co-authors are postdoctoral scholars Erin Gibson, PhD, Yujie Tang, PhD and Jai Pollepalli, PhD; undergraduate student Alyssa Noll; MD/PhD students Surya Nagaraja and Christopher Mount; Siddhartha Mitra, PhD, a senior scientist at the Stanford Institute for Stem Cell Biology and Regenerative Medicine; Pamelyn Woo, life science research assistant; Robert Malenka, MD, PhD, professor of psychiatry and behavioral sciences; Hannes Vogel, MD, professor of pathology and of pediatrics; and Parag Mallick, PhD, assistant professor of radiology. 
 
 Monje is also a member of Stanford’s Child Health Research Institute. 
 
 The study was funded by grants from the National Institute of Neurological Disorders and Stroke (grant K08NS070926); the McKenna Claire Foundation; the Matthew Larson Foundation; the National Science Foundation; the Godfrey Family Fund in Memory of Fiona Penelope; the California Institute for Regenerative Medicine; Alex’s Lemonade Stand Foundation; The Cure Starts Now; the Lyla Nsouli Foundation; the Dylan Jewett, Connor Johnson, Zoey Ganesh, Dylan Frick, Abigail Jensen, Wayland Villars, and Jennifer Kranz memorial funds; the Virginia and D.K. Ludwig Fund for Cancer Research; the Bear Necessities Pediatric Cancer Foundation; Lucile Packard Foundation for Children’s Health; the Child Health Research Institute at Stanford; and the Anne T. and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood Diseases. 
 
 Further information about Stanford’s Department of Neurology and Neurological Sciences, which also supported this work, is available at http://neurology.stanford.edu ||||| Treatments 
 
 Thoughts Can Fuel Some Deadly Brain Cancers 
 
 The simple act of thinking can accelerate the growth of many brain tumors. 
 
 That's the conclusion of a paper in Cell published Thursday that showed how activity in the cerebral cortex affected high-grade gliomas, which represent about 80 percent of all malignant brain tumors in people. 
 
 "This tumor is utilizing the core function of the brain, thinking, to promote its own growth," says Michelle Monje, a researcher and neurologist at Stanford who is the paper's senior author. 
 
 In theory, doctors could slow the growth of these tumors by using sedatives or other drugs to reduce mental activity, Monje says. But that's not a viable option because it wouldn't eliminate the tumor and "we don't want to stop people with brain tumors from thinking or learning or being active." 
 
 Even so, the discovery suggests other ways to slow down some of the most difficult brain tumors, says Tracy Batchelor, who directs the neuro-oncology program at Massachusetts General Hospital and was not involved in the research. 
 
 i itoggle caption Steve Fisch/Courtesy of Stanford School of Medicine Steve Fisch/Courtesy of Stanford School of Medicine 
 
 "We really don't have any curative treatments for high-grade gliomas," Batchelor says. The discovery of a link between tumor growth and brain activity "has opened up a window into potential therapeutic interventions," he says. 
 
 The discovery came from a team of scientists who studied human glioma tumors implanted in mouse brains. The scientists used a technique called optogenetics, which uses light to control brain cells, to increase the activity of cells near the tumors. 
 
 The team wanted to know whether this high level of activity would make the glioma grow more quickly. "And it turns out that it did," 
 
 The discovery of a link between tumor growth and brain activity is a byproduct of Monje's career-long quest to help to help children with a rare and deadly form of brain cancer. 
 
 The cancer is called diffuse intrinsic pontine glioma, or DIPG. Monje saw her first case when she was still in medical school. "I cared for a little girl who had diffuse intrinsic pontine glioma and I was just so struck by our failure to treat this disease," she says. 
 
 DIPG strikes about 200 children a year, often at around age 6. It can't be treated with surgery because the tumor cells become entwined with healthy cells in the brain stem. Children with DIPG typically live about nine months after they are diagnosed. 
 
 "This is a disease with a terrible prognosis," Monje says. "And it's one that unfortunately we haven't been able to touch with interventions for decades." 
 
 Monje wanted to change that. So after receiving her M.D. and Ph.D. from Stanford in 2004, she began studying DIPG tumor cells as well as the part of the brain in which they grow, the brain stem. 
 
 She began to suspect that this cancer was somehow hijacking a process called myelination, which happens in the brains of healthy kids. Myelination creates a layer of insulation around nerve fibers, which allows them to carry signals more quickly and efficiently. 
 
 Last year, Monje and a team of researchers showed that the cells responsible for myelination began to grow rapidly in response to high levels of brain activity. "That was an intriguing finding and it was consistent with our idea that activity in the brain, thinking, planning, using your brain, might be promoting the cancer arising within it," she says. 
 
 The mouse experiment confirmed Monje's suspicion. Another experiment showed that the glioma cells were indeed growing in response to the chemical signals that usually lead to myelination. 
 
 One striking finding, though, was that the link between brain activity and tumor growth wasn't limited to DIPG, the rare childhood tumor Monje had been studying since medical school. Her team found that a range of deadly gliomas grow faster when they're near highly active nerve cells. 
 
 "This work has much broader implications for brain tumors," says Batchelor. "It's not just pediatric tumors, it's pediatric and adult. And it's not just one particular type of glioma. This has potential implications across the entire family of gliomas in the brain." 
 
 Batchelor says Monje's research suggests a new way to slow down these tumors — by interrupting the pathways linking brain activity to tumor growth. 
 
 Monje says she is encouraged that her work has led to a better understanding of DIPG and other deadly childhood tumors. But she says it's still hard to feel gratified. 
 
 "It will be gratifying when we make some difference for these kids," she says.
– Thoughts can be deadly. So posits new research published this week in the journal Cell investigating the link between brain activity and tumor growth. Specifically, researchers at Stanford found that activity in the cerebral cortex promoted the growth of high-grade gliomas; they account for four out of every five malignant brain tumors, and a Stanford press release notes survival rates for those with the cancer have barely budged in the last three decades. To test the suspected link, the researchers implanted human glioma tumors into the brains of lab mice and then used light to increase brain-cell activity adjacent to those tumors. That increase did spur faster tumor growth, and the behavioral relationship—in which an organ's "primary function" fuels a tumor—is an unusual one. As lead author Michelle Monje puts it, "We don't think about ... breathing promoting the growth of lung cancer." Monje has spent more than a decade studying diffuse intrinsic pontine glioma, or DIPG, which exacts a cruel toll: It typically strikes around age 6, and it afflicts some 200 American kids each year; most are dead within nine months. (Earlier this month, the New Jersey Record shared the story of a family who donated 6-year-old Lily LaRue Anderson's tumor to Monje's team upon the girl's death; her battle with DIPG lasted 11 months.) A neuro-oncologist not involved in the study tells NPR that Monje's findings have "potential implications across the entire family of gliomas in the brain ... not just pediatric tumors" and could lead to new treatments. Monje tells NPR one route that's not an option: using sedatives to reduce brain activity. "We don't want to stop people with brain tumors from thinking or learning or being active." (Will tiny balls of gold help improve cancer treatments?)