Researchers at the Technical University of Munich report that pancreatic cancer nerve links form when cancer cells nerve-like connections called pseudosynapses to absorb glutamate and accelerate tumor growth, identifying a potential drug target that slowed tumors in mice.
Pancreatic cancer cells can “wire themselves” into the body’s nervous system to promote their own growth, scientists at the Technical University of Munich say, uncovering a mechanism that could open the door to new treatments for one of the deadliest cancers.
Researchers Identify Pseudosynapses in Tumor Samples
The research team found that pancreatic tumor cells form structures resembling synapses, the junctions that nerve cells use to communicate. These tumor structures, known as pseudosynapses, allow cancer cells to tap into neural signaling.
Pancreatic cancer is widely considered one of the most lethal malignancies because it is often diagnosed late and spreads quickly. Neural invasion — the growth of nerve fibers into tumors. It has long been linked to more aggressive disease and poorer outcomes.
About six years ago, U.S. scientists reported that certain brain tumors can form functional synapses to exploit neuronal signals. Inspired by that discovery, Professor Ekin Demir, a clinician scientist in the Department of Surgery at TUM University Hospital, and his colleagues investigated whether tumors outside the brain use similar tactics.
Pancreatic cancer was a prime candidate because neural invasion is especially common in this tumor type, the researchers said.
Analyzing human pancreatic tumor samples, the team searched for clusters of receptors that interact with neurotransmitters. In several samples, they found elevated levels of NMDA receptors, which bind the neurotransmitter glutamate, highlighting the presence of pancreatic cancer nerve links.
Electron microscopy revealed structures closely resembling synapses. Because these formations differ physiologically from normal neuronal synapses, the researchers termed them pseudosynapses.
Glutamate Triggers Calcium Waves That Drive Growth
The pancreas, like other glands, is regulated by the nervous system. In healthy tissue, glutamate signaling helps control cellular activity. The researchers found that pancreatic tumor cells exploit this mechanism.
“When glutamate binds to the cancer cells’ NMDA receptors, a channel opens, and calcium flows into the cell,” Demir said. “This influx triggers molecular signaling cascades that drive tumor growth and metastasis.”
The team observed that cancer cells produced slow, long-lasting calcium waves after glutamate stimulation. These sustained signals appear to promote tumor expansion and spread.
The findings suggest that pancreatic cancer nerve links allow the tumor to actively harness neural signals to fuel its progression rather than merely coexist with nearby nerves.
Drug Blocking NMDA Receptors Slows Tumors in Mice
In experiments involving mice, researchers administered a drug that blocks NMDA receptors on tumor cells. Tumors in treated animals grew more slowly, formed fewer metastases, and were linked to longer survival compared with untreated mice.
The drug used in the study was not identified as a new compound but as an existing agent capable of inhibiting NMDA receptor activity. Researchers are now using bioinformatic tools to identify approved drugs that may also block these specific receptors in pancreatic cancer cells.
“We are currently using bioinformatic methods to identify approved drugs that, in addition to their primary effects, can also block these specific NMDA receptors in pancreatic cancer cells,” Demir said. “Therapies targeting the interface between the nervous system and tumors could open up entirely new treatment options.”
The researchers caution that the findings are based on laboratory and animal studies. Clinical trials would be required to determine whether blocking NMDA receptors is safe and effective in patients.
The team also suspects that other tumor types may form pseudosynapses to accelerate growth, though further research is needed to confirm that possibility.
If validated in humans, pancreatic cancer nerve links could reshape understanding of how cancers interact with the nervous system and offer a new strategy against a disease with limited treatment options.
