2023年6月29日,

同一腦區的麵孔2023年6月28日來源:照片LIB /蓋蒂圖片社膠質母細胞瘤(GBM)是最激進的和致命的一種腦腫瘤。然而,潛在的分子機製推動GBM滲透並不完全理解。現在,來自貝勒醫學院的研究人員在動物模型中發現了一本小說過程神經元位置偏遠的原發腫瘤引起膠質母細胞瘤的基因表達的方式,隨後驅動腫瘤浸潤。“惡性腫瘤的腫瘤微環境中扮演著重要的角色,和神經元已成為腫瘤微環境的重要組成部分,促進腫瘤發生在許多癌症,”研究人員寫道。“最近研究GBM突出腫瘤和神經元之間的雙向信號傳播擴散的惡性循環,突觸整合,和大腦多動;然而,神經元亞型的身份和腫瘤亞種群駕駛這種現象不完全理解。在這裏,我們表明,胼胝體的投射神經元位於半球側初級GBM腫瘤促進發展和廣泛的滲透。”“以前的研究已經顯示“綠帶運動”的存在之間的聯係,在周圍腦區神經元活動增加,可促進腫瘤進展,”第一作者埃米特Huang-Hobbs博士說,他是一個研究生在實驗室的本傑明•迪尼,博士學位。研究神經元刺激GBM滲透,研究者們首先確定哪些神經元數量提升神經膠質瘤入侵。“切斷胼胝體消除神經元活動依賴性的GBM滲透加速度觀測與完整的控製,支持一個完整的胼胝體有必要促進神經膠質瘤進展和暗示尼共遠程預測在遠程駕駛GBM滲透,”Huang-Hobbs說。 “The findings suggest that GBMs receive neuronal inputs from a host of brain regions, implying that exposure to a diverse range of neuroactive compounds can potentially influence tumor growth. It’s now clear that tumor-neuron interactions are more widespread than previously thought,” said Deneen, professor and Russell J. and Marian K. Blattner chair in the department of neurosurgery, director of the Center for Cancer Neuroscience, and a member of the Dan L. Duncan Comprehensive Cancer Center at Baylor. He is also the corresponding author of the work. “In collaboration with the labs of Baylor researchers Jeffrey L. Noebels and Ganesh Rao, we found evidence suggesting that GBM and CPNs have a two-way conversation,” Huang-Hobbs said. “CPNs promote tumor infiltration, and the tumor affects neuronal connections or synapses. The tumor remodels local neuronal synapses and makes direct synaptic connections, raising the possibility that it alters brain circuit activity in these regions that are distant from the primary tumor.” Further analyses showed mechanistic details underlying these observations. The researchers found that the infiltrating tumor population is enriched for axon guidance genes, including SEMA4F, which they identified as an essential factor for glioma progression and neuronal activity-dependent infiltration. Interestingly, SEMA4F also promotes neuronal hyperactivity. The study demonstrates that subsets of neurons in locations remote to primary GBM promote malignant progression, and also show new mechanisms of glioma progression that are regulated by neuronal activity.