TY  - JOUR
AU  - Mäder, Lisa
AU  - Blank, Anna E
AU  - Capper, David
AU  - Jansong, Janina
AU  - Baumgarten, Peter
AU  - Wirsik, Naita M
AU  - Zachskorn, Cornelia
AU  - Ehlers, Jakob
AU  - Seifert, Michael
AU  - Klink, Barbara
AU  - Liebner, Stefan
AU  - Niclou, Simone
AU  - Naumann, Ulrike
AU  - Harter, Patrick N
AU  - Mittelbronn, Michel
TI  - Pericytes/vessel-associated mural cells (VAMCs) are the major source of key epithelial-mesenchymal transition (EMT) factors SLUG and TWIST in human glioma.
JO  - OncoTarget
VL  - 9
IS  - 35
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2018-02315
SP  - 24041-24053
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29844871
C2  - pmc:PMC5963615
DO  - DOI:10.18632/oncotarget.25275
UR  - https://inrepo02.dkfz.de/record/142085
ER  -