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@ARTICLE{Lokumcu:287027,
      author       = {T. Lokumcu$^*$ and M. Iskar and M. Schneider$^*$ and D.
                      Helm$^*$ and G. Klinke and L. Schlicker$^*$ and F.
                      Bethke$^*$ and G. Müller$^*$ and K. Richter$^*$ and G.
                      Poschet and E. Phillips$^*$ and V. Goidts$^*$},
      title        = {{P}roteomic, {M}etabolomic, and {F}atty {A}cid {P}rofiling
                      of {S}mall {E}xtracellular {V}esicles from {G}lioblastoma
                      {S}tem-{L}ike {C}ells and {T}heir {R}ole in {T}umor
                      {H}eterogeneity.},
      journal      = {ACS nano},
      volume       = {18},
      number       = {3},
      issn         = {1936-0851},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DKFZ-2024-00134},
      pages        = {2500-2519},
      year         = {2024},
      note         = {#EA:B067#LA:B067# / 2024 Jan 23;18(3):2500-2519},
      abstract     = {Glioblastoma is a deadly brain tumor for which there is no
                      cure. The presence of glioblastoma stem-like cells (GSCs)
                      contributes to the heterogeneous nature of the disease and
                      makes developing effective therapies challenging.
                      Glioblastoma cells have been shown to influence their
                      environment by releasing biological nanostructures known as
                      extracellular vesicles (EVs). Here, we investigated the role
                      of GSC-derived nanosized EVs (<200 nm) in glioblastoma
                      heterogeneity, plasticity, and aggressiveness, with a
                      particular focus on their protein, metabolite, and fatty
                      acid content. We showed that conditioned medium and small
                      extracellular vesicles (sEVs) derived from cells of one
                      glioblastoma subtype induced transcriptomic and proteomic
                      changes in cells of another subtype. We found that
                      GSC-derived sEVs are enriched in proteins playing a role in
                      the transmembrane transport of amino acids, carboxylic
                      acids, and organic acids, growth factor binding, and
                      metabolites associated with amino acid, carboxylic acid, and
                      sugar metabolism. This suggests a dual role of GSC-derived
                      sEVs in supplying neighboring GSCs with valuable metabolites
                      and proteins responsible for their transport. Moreover,
                      GSC-derived sEVs were enriched in saturated fatty acids,
                      while their respective cells were high in unsaturated fatty
                      acids, supporting that the loading of biological cargos into
                      sEVs is a highly regulated process and that GSC-derived sEVs
                      could be sources of saturated fatty acids for the
                      maintenance of glioblastoma cell metabolism. Interestingly,
                      sEVs isolated from GSCs of the proneural and mesenchymal
                      subtypes are enriched in specific sets of proteins,
                      metabolites, and fatty acids, suggesting a molecular
                      collaboration between transcriptionally different
                      glioblastoma cells. In summary, this study revealed the
                      complexity of GSC-derived sEVs and unveiled their potential
                      contribution to tumor heterogeneity and critical cellular
                      processes commonly deregulated in glioblastoma.},
      keywords     = {exosomes (Other) / fatty acids (Other) / glioblastoma
                      (Other) / glioblastoma stem-like cells (Other) /
                      metabolomics (Other) / proteomics (Other) / small
                      extracellular vesicles (Other)},
      cin          = {B067 / W120 / W230},
      ddc          = {540},
      cid          = {I:(DE-He78)B067-20160331 / I:(DE-He78)W120-20160331 /
                      I:(DE-He78)W230-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38207106},
      doi          = {10.1021/acsnano.3c11427},
      url          = {https://inrepo02.dkfz.de/record/287027},
}