Tomasz Pienkowski, Patrycja Mojsak, Tomasz Kowalczyk, Dominik Cysewski, Mikolaj Krupa, Robert Rutkowski, Zenon Mariak, Adrian Godlewski, Joanna Reszec, Marcin Moniuszko, Adam Kretowski, Tomasz Lyson, Michal Ciborowski
{"title":"Proteomic profiling reveals dynamic regulation of vesicle trafficking across glioma grades.","authors":"Tomasz Pienkowski, Patrycja Mojsak, Tomasz Kowalczyk, Dominik Cysewski, Mikolaj Krupa, Robert Rutkowski, Zenon Mariak, Adrian Godlewski, Joanna Reszec, Marcin Moniuszko, Adam Kretowski, Tomasz Lyson, Michal Ciborowski","doi":"10.1007/s11060-025-05151-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"585-598"},"PeriodicalIF":3.1000,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420692/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuro-Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11060-025-05151-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/24 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
