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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},
}