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@ARTICLE{Mder:142085,
author = {L. Mäder and A. E. Blank and D. Capper$^*$ and J. Jansong
and P. Baumgarten and N. M. Wirsik and C. Zachskorn$^*$ and
J. Ehlers and M. Seifert and B. Klink and S. Liebner and S.
Niclou and U. Naumann and P. N. Harter$^*$ and M.
Mittelbronn$^*$},
title = {{P}ericytes/vessel-associated mural cells ({VAMC}s) are the
major source of key epithelial-mesenchymal transition
({EMT}) factors {SLUG} and {TWIST} in human glioma.},
journal = {OncoTarget},
volume = {9},
number = {35},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2018-02315},
pages = {24041-24053},
year = {2018},
abstract = {Epithelial-to-mesenchymal transition (EMT) is supposed to
be responsible for increased invasion and metastases in
epithelial cancer cells. The activation of EMT genes has
further been proposed to be important in the process of
malignant transformation of primary CNS tumors. Since the
cellular source and clinical impact of EMT factors in
primary CNS tumors still remain unclear, we aimed at
deciphering their distribution in vivo and
clinico-pathological relevance in human gliomas. We
investigated 350 glioma patients for the expression of the
key EMT factors SLUG and TWIST by immunohistochemistry and
immunofluorescence related to morpho-genetic alterations
such as EGFR-amplification, IDH-1 (R132H) mutation and
1p/19q LOH. Furthermore, transcriptional cluster and
survival analyses were performed. Our data illustrate that
SLUG and TWIST are overexpressed in gliomas showing vascular
proliferation such as pilocytic astrocytomas and
glioblastomas. EMT factors are exclusively expressed by
non-neoplastic pericytes/vessel-associated mural cells
(VAMCs). They are not associated with patient survival but
correlate with pericytic/VAMC genes in glioblastoma cluster
analysis. In summary, the upregulation of EMT genes in
pilocytic astrocytomas and glioblastomas reflects the level
of activation of pericytes/VAMCs in newly formed blood
vessels. Our results underscore that the negative prognostic
potential of the EMT signature in the group of diffuse
gliomas of WHO grade II-IV does most likely not derive from
glioma cells but rather reflects the degree of proliferating
mural cells thereby constituting a potential target for
future alternative treatment approaches.},
cin = {G380},
ddc = {610},
cid = {I:(DE-He78)G380-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29844871},
pmc = {pmc:PMC5963615},
doi = {10.18632/oncotarget.25275},
url = {https://inrepo02.dkfz.de/record/142085},
}