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  3. Comparative proteomic profiling of glioblastoma and healthy brain cell-derived extracellular vesicles reveals enrichment of cancer-associated proteins

Comparative proteomic profiling of glioblastoma and healthy brain cell-derived extracellular vesicles reveals enrichment of cancer-associated proteins

  • J Proteomics. 2025 Mar 7:316:105418. doi: 10.1016/j.jprot.2025.105418.
Hope K Hutson 1,  Guoting Qin 2,  Chengzhi Cai 3,  Gergana G Nestorova 4
Affiliations

Affiliations

  • 1 Molecular Science and Nanotechnology, Louisiana Tech University, United States.
  • 2 College of Optometry, University of Houston, United States.
  • 3 Department of Chemistry, University of Houston, United States.
  • 4 School of Biological Sciences, Louisiana Tech University, United States. Electronic address: ggnestor@latech.edu.
PMID: 40058457 DOI: 10.1016/j.jprot.2025.105418
Abstract

Extracellular vesicles (EVs)-mediated cellular communication plays a role in Cancer development and progression. This study focuses on identifying glioblastoma-specific EV protein markers through a comparative mass spectrometry bottom-up proteomic analysis of the LN-229 cell line and human neurons, astrocytes, and endothelial brain cells (HEBCs) using timsTOF Pro 2 instrument. The statistically significant upregulated proteins with fold change greater than 2 in the glioblastoma-derived EVs were clustered based on physical and functional interactions using the STRING database and analyzed using Gene Ontology enrichment. LN229-derived EVs contained an average of 2635 proteins, while human astrocytes, neurons, and HEBC encapsulated 2647, 716, and 2285 proteins, respectively. NanoParticle Tracking Analysis indicated that glioblastoma-derived EVs exhibited greater size variability compared to EVs from healthy cells. Statistical analysis identified 25 statistically significant proteins with increased levels in LN229 EVs relative to at least two healthy cell lines suggesting their potential as glioblastoma markers. Functional clustering using the STRING database and GO analysis indicated involvement in epigenetic regulation, metastasis, angiogenesis, and protein folding. Post-translational modification analysis identified a subset of 17 proteins unique to the cancer-derived EVs involved in chromatin regulation, extracellular matrix remodeling, and basement membrane organization pathways, highlighting their role in tumor progression.

Keywords

Extracellular vesicles; Glioblastoma; Mass spectrometry.

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