Li Yang, Wang Yao, Han Xingyue, Xu Jing, Liu Enyu, Cheng Jingmin, Ma Yuan, Yang Tao, Wu Jianping, Sun Haodong, Fan Kexia, Shen Danyi, Li Jie, Chen Xin, Yu Sixun, Shu Haifeng
Department of Neurosurgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China.
Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, 200092, China.
J Neurooncol. 2025 Apr 14. doi: 10.1007/s11060-025-05007-y.
Gliomas are the most common type of primary malignant brain tumor with high degree of malignancy and rapid progression, and patients often have complications such as epilepsy and cognitive impairment. Thus, identifying related therapeutic targets, prolonging patient survival time and improving patient quality of life are urgently needed. Recent studies have shown that glutamatergic neurons around tumors and glioma cells form synapses, neuron-glioma synapses (NGSs), which have electrophysiological properties and participate in the proliferation, infiltration and invasion of tumors. Therefore, we aimed to explore the molecular mechanisms underlying NGS formation.
We used bioinformatic analysis to screen for the expression of SPARCL1, which may play a role in promoting NGS formation, and we evaluated clinical samples through immunofluorescence, Western blot, and reverse transcriptase polymerase chain reaction (RT‒PCR) assays to validate the bioinformatic analysis results. Vitro neuron-glioma cell coculture model was established and allowed us to edit SPARCL1 expression in glioma cells, further allowing us to investigate the role of SPARCL1 in NGS formation.
Bioinformatic analysis revealed that SPARCL1 is highly expressed in glioma cells and is associated with synaptogenesis. Clinical samples were evaluated to verify the bioinformatics results, and SPARCL1 was found to be highly distributed in the tumor peripheral region. In the vitro neuron-glioma cell coculture model, NGSs were clearly observed, and SPARCL1 overexpression promoted NGS formation.
Taken together, these findings suggest that SPARCL1 is one of the molecules that promotes NGS formation in the tumor peripheral region.
胶质瘤是最常见的原发性恶性脑肿瘤，恶性程度高且进展迅速，患者常伴有癫痫和认知障碍等并发症。因此，迫切需要确定相关治疗靶点、延长患者生存时间并提高患者生活质量。最近的研究表明，肿瘤周围的谷氨酸能神经元与胶质瘤细胞形成突触，即神经元 - 胶质瘤突触（NGS），其具有电生理特性并参与肿瘤的增殖、浸润和侵袭。因此，我们旨在探索NGS形成的分子机制。
我们使用生物信息学分析来筛选可能在促进NGS形成中起作用的SPARCL1的表达，并通过免疫荧光、蛋白质免疫印迹和逆转录聚合酶链反应（RT - PCR）分析评估临床样本，以验证生物信息学分析结果。建立体外神经元 - 胶质瘤细胞共培养模型，使我们能够编辑胶质瘤细胞中SPARCL1的表达，进而研究SPARCL1在NGS形成中的作用。
生物信息学分析显示，SPARCL1在胶质瘤细胞中高表达且与突触发生相关。对临床样本进行评估以验证生物信息学结果，发现SPARCL1在肿瘤周边区域高度分布。在体外神经元 - 胶质瘤细胞共培养模型中，清晰观察到了NGS，并且SPARCL1过表达促进了NGS的形成。
综上所述，这些发现表明SPARCL1是促进肿瘤周边区域NGS形成的分子之一。
