无感受神经元通过CGRP-RAMP1轴促进胃瘤的进展
Xiaofei Zhi1,2, Feijing Wu1, Jin Qian1
1Division of Digestive and Liver Diseases, Irving Cancer Research Center, Columbia University Medical Center, New York, NY, USA.
Nature
|February 19, 2025
概括
胃癌利用周围感官神经进行生长和扩散. 针对这些癌症神经连接,特别是使用CGRP抑制剂,提供了一个有前途的新治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
背景情况:
- 癌细胞可以利用神经元生存和生长.
- 神经回路与中枢神经系统癌症有关.
- 周围神经系统在胃癌中的参与仍然不太了解.
研究的目的:
- 为了研究外周神经和胃癌之间的相互作用.
- 为了确定涉及的特定类型的感觉神经元.
- 探索向癌症神经通信的治疗潜力.
主要方法:
- 利用了胃癌的小鼠模型.
- 使用神经追踪技术.
- 已建立的3D共文化系统.
- 应用化学遗传学和光遗传学用于神经元操纵.
- 研究了针对感官神经元和CGRP的药理干预措施.
主要成果:
- 无感应神经,主要是CGRP + 类神经元,以NGF依赖的方式广泛内化胃瘤.
- 感觉神经元与胃癌球体直接连接.
- 感觉神经元的激活促进了瘤的生长和转移,通过癌细胞中的信号传递.
- 抑制感觉神经元或CGRP抑制了瘤进展和改善了生存率.
- 证明了一种功能性癌细胞-基神经回路.
结论:
- 在胃癌中建立了一个新的癌细胞-外周感官神经元电路.
- 突出了CGRP+类神经元在促进胃瘤生长和转移中的作用.
- 确定了癌症神经通路作为胃癌治疗的潜在治疗标.
相关概念视频
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
147
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates...
147
Neural Regulation
39.1K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.1K
Nociception
27.7K
Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
27.7K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.1K
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
Pathophysiology of Peptic Ulcer Disease: Injurious Factors
524
Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
524


