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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Lisa Mäder - , Johann Wolfgang Goethe-Universität Frankfurt am Main (Autor:in)
  • Anna E. Blank - , Johann Wolfgang Goethe-Universität Frankfurt am Main (Autor:in)
  • David Capper - , Universität Heidelberg, Deutsches Krebsforschungszentrum (DKFZ), Charité – Universitätsmedizin Berlin (Autor:in)
  • Janina Jansong - , Eberhard Karls Universität Tübingen (Autor:in)
  • Peter Baumgarten - , Johann Wolfgang Goethe-Universität Frankfurt am Main (Autor:in)
  • Naita M. Wirsik - , Johann Wolfgang Goethe-Universität Frankfurt am Main (Autor:in)
  • Cornelia Zachskorn - , Johann Wolfgang Goethe-Universität Frankfurt am Main, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Jakob Ehlers - , Charité – Universitätsmedizin Berlin, Eberhard Karls Universität Tübingen (Autor:in)
  • Michael Seifert - , Nationales Centrum für Tumorerkrankungen (Partner: UKD, MFD, HZDR, DKFZ), Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Barbara Klink - , Institut für Klinische Genetik, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Stefan Liebner - , Johann Wolfgang Goethe-Universität Frankfurt am Main (Autor:in)
  • Simone Niclou - , Luxembourg Institute of Health (Autor:in)
  • Ulrike Naumann - , Eberhard Karls Universität Tübingen (Autor:in)
  • Patrick N. Harter - , Johann Wolfgang Goethe-Universität Frankfurt am Main, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Michel Mittelbronn - , Johann Wolfgang Goethe-Universität Frankfurt am Main, Deutsches Krebsforschungszentrum (DKFZ), Luxembourg Institute of Health, Luxembourg Centre of Neuropathology (LCNP), Laboratoire National de Santé, University of Luxembourg (Autor:in)

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 morphogenetic 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.

Details

OriginalspracheEnglisch
Seiten (von - bis)24041-24053
Seitenumfang13
FachzeitschriftOncotarget
Jahrgang9
Ausgabenummer35
PublikationsstatusVeröffentlicht - 8 Mai 2018
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC5963615
Scopus 85046801379
ORCID /0000-0002-2844-053X/work/153655332

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • EMT, Gliomas, MET, Pericytes, Vessel-associated mural cells