Pienkowski Tomasz, Mojsak Patrycja, Kowalczyk Tomasz, Cysewski Dominik, Krupa Mikolaj, Rutkowski Robert, Mariak Zenon, Godlewski Adrian, Reszec Joanna, Moniuszko Marcin, Kretowski Adam, Lyson Tomasz, Ciborowski Michal
Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bialystok, M. Sklodowskiej-Curie 24A, Bialystok, 15-276, Poland.
Department of Neurosugery, Medical University of Bialystok, Bialystok, 15-276, Poland.
J Neurooncol. 2025 Jul 24. doi: 10.1007/s11060-025-05151-5.
Gliomas are highly heterogeneous central nervous system tumors that evolve through progressive molecular reprogramming. While cell proliferation and adhesion mechanisms are well-characterized, the contribution of vesicle trafficking to glioma progression remains underexplored. This study aimed to characterize proteomic changes across glioma grades.
We performed untargeted, quantitative proteomic profiling of glioma tissues across WHO grades I-IV using a combination of Tandem Mass Tag (TMT)-11plex labeling and high-resolution liquid chromatography-mass spectrometry (LC-MS). Tissue samples were processed using filter-aided sample preparation (FASP) and analyzed using a µPAC reverse-phase HPLC system coupled to a high-resolution mass spectrometer. Protein identification and quantification were conducted through database searching and validated against stringent quality control criteria.
We identified over 4,400 proteins across samples, revealing dynamic, grade-specific shifts in vesicle trafficking. Grade II gliomas showed upregulation of exocytic proteins (e.g., synaptotagmin, syntaxin, clathrin) and suppression of dynamin, suggesting enhanced vesicular secretion. Grade III tumors exhibited the opposite trend-marked downregulation of exocytic components with concurrent activation of clathrin-mediated endocytosis. Grade IV gliomas displayed a hybrid profile, with partial reactivation of exocytic machinery alongside sustained endocytic activity, indicative of vesicular plasticity.
This study highlights the synaptic vesicle cycle as a progressively remodeled pathway in glioma biology. Our findings suggest that vesicle trafficking is a critical, underrecognized feature of glioma pathogenesis and may represent a novel axis for therapeutic exploration.
胶质瘤是高度异质性的中枢神经系统肿瘤，通过渐进性分子重编程演变。虽然细胞增殖和黏附机制已得到充分表征，但囊泡运输对胶质瘤进展的作用仍未得到充分探索。本研究旨在表征不同级别胶质瘤的蛋白质组学变化。
我们使用串联质谱标签（TMT）-11重标记和高分辨率液相色谱-质谱联用（LC-MS）相结合的方法，对世界卫生组织（WHO）I-IV级的胶质瘤组织进行了非靶向定量蛋白质组分析。组织样本采用滤膜辅助样品制备（FASP）方法处理，并使用与高分辨率质谱仪联用的µPAC反相高效液相色谱系统进行分析。通过数据库搜索进行蛋白质鉴定和定量，并根据严格的质量控制标准进行验证。
我们在样本中鉴定出4400多种蛋白质，揭示了囊泡运输中动态的、特定级别的变化。II级胶质瘤显示胞吐蛋白（如突触结合蛋白、 syntaxin、网格蛋白）上调，动力蛋白受到抑制，提示囊泡分泌增强。III级肿瘤呈现相反的趋势——胞吐成分明显下调，同时网格蛋白介导的内吞作用激活。IV级胶质瘤表现出混合特征，胞吐机制部分重新激活，同时内吞活性持续存在，表明囊泡具有可塑性。
本研究强调突触囊泡循环是胶质瘤生物学中一个逐渐重塑的途径。我们的研究结果表明，囊泡运输是胶质瘤发病机制中一个关键但未被充分认识的特征，可能代表了一个新的治疗探索轴。
