Brain Tumor Res Treat.  2022 Oct;10(4):207-214. 10.14791/btrt.2022.0031.

Proteomics of Extracellular Vesicle in Glioblastoma

• Lee YJ
• Seo CW
• Lee D
• Choi D

• KMID: 2534718
• DOI: http://doi.org/10.14791/btrt.2022.0031

Abstract

Glioblastoma multiforme (GBM), a high-grade astrocytic brain tumor, has highly aggressive and heterogeneous phenotypes with active cellular invasion, angiogenesis, and immune system modulation in the tumor microenvironment driven by complex oncogenic mutations. This abnormal disease progression could be attributed to extracellular vesicles (EVs) containing diverse bioactive molecules, including proteins, genetic materials, lipids, and metabolites. Importantly, GBM-related EVs have emerged as key mediators in cancer progression, acting as carriers for the transfer of oncogenic proteins such as epidermal growth factor receptor variant III (EGFRvIII) and genetic materials (DNA and RNA). Remarkably, recent progress in EV analysis has enabled its purification with high confidence by estimating the purity level of isolated EVs. Thus, mass spectrometry-based proteomic analysis could generate highly reliable vesicular proteomes. Glioblastoma EV proteome studies have revealed the specific increase in vesicular protein cargo due to their oncogenic transformation, and these EV proteins are closely associated with cancer invasion. Moreover, their proteomic data reflects the molecular alterations that occur in parental GBM and provides potent diagnostic information in a minimally invasive manner in liquid biopsy. Thus, proteomic analysis of GBM EVs could provide an increased understanding of their biological properties and activity in the GBM microenvironment, and provide significant implications for advanced approaches in the diagnosis of these intractable tumors.

Keyword

Glioblastoma; Exosomes; Proteomics; Neoplasm Invasiveness; Diagnosis

Figure

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  Fig. 1 Overview of methodological approaches to isolate EV for proteomics. Density gradient ultracentrifuge is considered the gold-standard method in EV proteomics. The purity of EVs could be estimated by particle number per protein amount as suggested by Webber and Clayton [37]. EV, extracellular vesicle; CSF, cerebrospinal fluid; NTA, nanoparticle tracking analysis; TRPS, tunable resistive pulse sensing.

• 

  Fig. 2 EV subtypes and heterogeneity. Glioblastoma cell releases both ectosomes and exosomes. Oncogenic transformation during GBM progression alters the single EV distribution with different proteomic compositions related to cancer invasion. Moreover, because released EVs from glioblastoma cells represent the status of parental cells, decoding of EV heterogeneity and complexity by a single EV analysis could be applied in the diagnosis against GBM. EV, extracellular vesicle; GBM, glioblastoma multiforme; MVB, multivesicular body; BSG, basigin; ECM, extracellular matrix.

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