gms | German Medical Science

67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12. - 15. Juni 2016, Frankfurt am Main

Loss of endothelial programmed cell death 10 (PDCD10) promotes glioblastoma in vitro and in vivo

Meeting Abstract

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  • Yuan Zhu - Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany
  • Kai Zhao - Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany
  • Kathy Keyvani - Institute of Neuropathology, University of Duisburg-Essen, Essen, Germany
  • Nicole Lambertz - Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany
  • Ulrich Sure - Department of Neurosurgery, University of Duisburg-Essen, Essen, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMI.02.06

doi: 10.3205/16dgnc239, urn:nbn:de:0183-16dgnc2392

Veröffentlicht: 8. Juni 2016

© 2016 Zhu et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Neo-angiogenesis is a hallmark of glioblastoma (GBM), which is sustained by autocrine and paracrine interactions between neoplastic and non-neoplastic cells. Programmed cell death 10 (PDCD10) is ubiquitously expressed in nearly all tissues and plays crucial roles in regulating angiogenesis and apoptosis. Recently we discovered the absence of PDCD10 expression in the tumor vessels of GBM patients, which raised the hypothesis that loss of endothelial PDCD10 altered GBM cell phenotyping and affected tumor progression.

Method: Endothelial PDCD10 was silenced by siRNA and by lentiviral shRNA. Tumor cell phenotype was studied in direct- and indirect-co-culture of endothelial cells (ECs) with U87 or with LN229 cells. Angiogenic protein array was performed in the media of PDCD10-silenced ECs. Tumor angiogenesis and tumor growth were investigated in a human GBM xenograft mouse model.

Results: Endothelial silence of PDCD10 significantly stimulated tumor cell proliferation, migration, adhesion and invasion, and inhibited apoptosis in co-cultures. Stable knockdown of endothelial PDCD10 increased the microvessel density and the formation of functional vascular network, and led to a 4-fold larger tumor mass in mice. Intriguingly, endothelial deletion of PDCD10 increased (more than 2-fold) the release of 20 of 55 tested pro-angiogenic factors, which in turn activated Erk1/2 and Akt in GBM cells.

Conclusions: We provide evidence for the first time that loss of endothelial PDCD10 activates GBM cells and promotes tumor growth most likely via a paracrine mechanism. PDCD10 shows a tumor-suppressor-like function in the cross-talk between ECs and tumor cells and is potentially implicated in the progression of GBM.