Glioblastoma‐derived extracellular vesicles modify the phenotype of monocytic cells

2015/03/20 by Jeroen de Vrij, Sybren L. N. Maas, S.L. Niek Maas +18 · 200 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · Medicine · #Biology #Cancer research #Cell biology #Chemistry #Extracellular #Extracellular vesicles #Extracellular vesicles in disease #Gene #Genetics #Glioblastoma #Immune cells in cancer #Medicine #MicroRNA in disease regulation #Pathology #Phenotype

paper · pdf · doi:10.1002/ijc.29521

published in International Journal of Cancer 137(7), 1630-1642 (Wiley)

openalex publication_date 2015/03/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumor and is without exception lethal. GBMs modify the immune system, which contributes to the aggressive nature of the disease. Particularly, cells of the monocytic lineage, including monocytes, macrophages and microglia, are affected. We investigated the influence of GBM-derived extracellular vesicles (EVs) on the phenotype of monocytic cells. Proteomic profiling showed GBM EVs to be enriched with proteins functioning in extracellular matrix interaction and leukocyte migration. GBM EVs appeared to skew the differentiation of peripheral blood-derived monocytes to alternatively activated/M2-type macrophages. This was observed for EVs from an established cell line, as well as for EVs from primary cultures of GBM stem-like cells (GSCs). Unlike EVs of non-GBM origin, GBM EVs induced modified expression of cell surface proteins, modified cytokine secretion (e.g., an increase in vascular endothelial growth factor and IL-6) and increased phagocytic capacity of the macrophages. Most pronounced effects were observed upon incubation with EVs from mesenchymal GSCs. GSC EVs also affected primary human microglia, resulting in increased expression of Membrane type 1-matrix metalloproteinase, a marker for GBM microglia and functioning as tumor-supportive factor. In conclusion, GBM-derived EVs can modify cells of the monocytic lineage, which acquire characteristics that resemble the tumor-supportive phenotypes observed in patients.

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