Pericytes/vessel-associated mural cells (VAMCs) are the major source of key epithelial-mesenchymal transition (EMT) factors SLUG and TWIST in human glioma

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 proc
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.
show moreshow less

Metadaten
Author:Lisa Mäder, Anna-Eva Blank, David Capper, Janina Jansong, Peter Baumgarten, Naita M. Wirsik, Cornelia Zachskorn, Jakob Ehlers, Michael Seifert, Barbara Klink, Stefan Liebner, Simone P. Niclou, Ulrike Naumann, Patrick Nikolaus Harter, Michel Guy André Mittelbronn
URN:urn:nbn:de:hebis:30:3-465718
DOI:http://dx.doi.org/10.18632/oncotarget.25275
ISSN:1949-2553
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29844871
Parent Title (English):OncoTarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/05/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/06/07
Tag:EMT; MET; gliomas; pericytes; vessel-associated mural cells
Volume:9
Issue:35
Pagenumber:13
First Page:24041
Last Page:24053
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS PPN:433826657
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

$Rev: 11761 $