Exp Neurobiol.  2021 Apr;30(2):120-143. 10.5607/en21004.

Tumor Spheroids of an Aggressive Form of Central Neurocytoma Have Transit-Amplifying Progenitor Characteristics with Enhanced EGFR and Tumor Stem Cell Signaling

Affiliations
  • 1Department of Neurosurgery, Seoul National University College of Medicine, Seoul 03082, Korea
  • 2Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Korea
  • 3Department of Neurophysiology, Seoul National University College of Medicine, Seoul 03082, Korea
  • 4Smart Healthcare Medical Device Research Center, Samsung Medical Center, Seoul 06351, Korea
  • 5Department of Pathology, Seoul National University College of Medicine, Seoul 03082, Korea
  • 6Ischemic/Hypoxic Disease Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03082, Korea
  • 7Clinical Research Institute, Seoul National University Hospital, Seoul 03082, Korea

Abstract

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

Keyword

Central neurocytoma; Tumor spheroids; Subventricular zone; Neural stem cell; Transit-amplifying cells; Radial glia cells; Gene Set Enrichment Analysis
Full Text Links
  • EN
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error