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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Lisa Mäder - , Goethe University Frankfurt a.M. (Author)
  • Anna E. Blank - , Goethe University Frankfurt a.M. (Author)
  • David Capper - , Heidelberg University , German Cancer Research Center (DKFZ), Charité – Universitätsmedizin Berlin (Author)
  • Janina Jansong - , University of Tübingen (Author)
  • Peter Baumgarten - , Goethe University Frankfurt a.M. (Author)
  • Naita M. Wirsik - , Goethe University Frankfurt a.M. (Author)
  • Cornelia Zachskorn - , Goethe University Frankfurt a.M., German Cancer Research Center (DKFZ) (Author)
  • Jakob Ehlers - , Charité – Universitätsmedizin Berlin, University of Tübingen (Author)
  • Michael Seifert - , National Center for Tumor Diseases (Partners: UKD, MFD, HZDR, DKFZ), Institute for Medical Informatics and Biometry (Author)
  • Barbara Klink - , Institute of Clinical Genetics, University Hospital Carl Gustav Carus Dresden (Author)
  • Stefan Liebner - , Goethe University Frankfurt a.M. (Author)
  • Simone Niclou - , Luxembourg Institute of Health (Author)
  • Ulrike Naumann - , University of Tübingen (Author)
  • Patrick N. Harter - , Goethe University Frankfurt a.M., German Cancer Research Center (DKFZ) (Author)
  • Michel Mittelbronn - , Goethe University Frankfurt a.M., German Cancer Research Center (DKFZ), Luxembourg Institute of Health, Luxembourg Centre of Neuropathology (LCNP), Laboratoire National de Santé, University of Luxembourg (Author)

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

Original languageEnglish
Pages (from-to)24041-24053
Number of pages13
JournalOncotarget
Volume9
Issue number35
Publication statusPublished - 8 May 2018
Peer-reviewedYes

External IDs

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

Keywords

Sustainable Development Goals

Keywords

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