Recent research has shown that cancer cells can interact with neurons to promote their own survival and growth. In the central nervous system, it was already known that cancer can form neural circuits, but now, scientists have identified a new pattern of connection between the peripheral nervous system and gastric cancer, or stomach cancer.
In recent years, scientists have discovered that cancer cells not only grow uncontrollably, but can also interact with neurons, the cells in the nervous system responsible for transmitting signals in the body.
This connection between cancer and nerves can help tumors grow, spread, and even resist treatment. Some types of cancer can “communicate” with neurons, activating pathways that favor their growth and make the disease more aggressive.
Understanding this relationship paves the way for new therapeutic strategies that seek to block this communication and thus hinder the progression of cancer.
Recent research has shown that cancer cells can interact with neurons to promote their own survival and growth. In the central nervous system, it was already known that cancer can form neural circuits, but now, scientists have identified a new pattern of connection between the peripheral nervous system and gastric cancer, that is, stomach cancer.
In studies with mice that developed gastric cancer, it was observed that certain nerves, called nociceptive nerves (responsible for transmitting pain signals), grew rapidly around the tumor.
This growth was driven by a molecule known as NGF (neuron growth factor). In addition, researchers identified that the main neurons involved in this process were of the CGRP+ type, which are part of the gastric sensory system.
CGRP+ neurons are nerve cells that produce and release a substance called calcitonin gene-related peptide (CGRP). This peptide plays an important role in transmitting pain signals, controlling blood flow, and other functions in the body.
These neurons are involved in sensory processes, such as the perception of pain in the stomach, and recent studies suggest that they may also influence the growth of certain types of cancer by communicating directly with tumor cells.
To better understand this connection, scientists created a three-dimensional cell culture model in which sensory neurons were placed alongside gastric cancer cells. The study revealed that these nerve cells connected directly to the tumors, establishing active communication.
When the sensory neurons were chemically stimulated, this caused an increase in calcium levels within the cancer cells. This process activated mechanisms that stimulated tumor growth and facilitated the spread of the cancer to other parts of the body (metastasis).
Example of cancer cells (green) in contact with sensory neurons (magenta).
On the other hand, when the researchers blocked the action of sensory neurons with drugs or inhibited the substance CGRP, tumor growth slowed and the mice lived longer.
In another experiment, the scientists used light to directly activate the tumors (a technique called optogenetics) and observed that this increased the flow of calcium in a specific area of the brain called the jugular nucleus, resulting in the release of CGRP.
This finding confirms the existence of a functional circuit between neurons and gastric cancer, showing that this communication could be a target for new cancer treatments.
These findings are important because they reveal that sensory neurons are not just passive spectators of cancer, but rather active participants that directly influence the development of the disease. By blocking this interaction, it may be possible to slow or even prevent the progression of gastric cancer, opening up new possibilities for innovative therapies.
READ MORE:
Nociceptive neurons promote gastric tumour progression via a CGRP–RAMP1 axis
Xiaofei Zhi, Feijing Wu, Jin Qian, Yosuke Ochiai, Guodong Lian, Ermanno Malagola, Biyun Zheng, Ruhong Tu, Yi Zeng, Hiroki Kobayashi, Zhangchuan Xia, Ruizhi Wang, Yueqing Peng, Qiongyu Shi, Duan Chen, Sandra W. Ryeom and Timothy C. Wang
Nature. 19 February 2025
DOI: 10.1038/s41586-025-08591-1
Abstract:
Cancer cells have been shown to exploit neurons to modulate their survival and growth, including through the establishment of neural circuits within the central nervous system1,2,3. Here we report a distinct pattern of cancer–nerve interactions between the peripheral nervous system and gastric cancer. In multiple mouse models of gastric cancer, nociceptive nerves demonstrated the greatest degree of nerve expansion in an NGF-dependent manner. Neural tracing identified CGRP+ peptidergic neurons as the primary gastric sensory neurons. Three-dimensional co-culture models showed that sensory neurons directly connect with gastric cancer spheroids. Chemogenetic activation of sensory neurons induced the release of calcium into the cytoplasm of cancer cells, promoting tumour growth and metastasis. Pharmacological ablation of sensory neurons or treatment with CGRP inhibitors suppressed tumour growth and extended survival. Depolarization of gastric tumour membranes through in vivo optogenetic activation led to enhanced calcium flux in jugular nucleus complex and CGRP release, defining a cancer cell–peptidergic neuronal circuit. Together, these findings establish the functional connectivity between cancer and sensory neurons, identifying this pathway as a potential therapeutic target.
Comments