Oligodendrocyte Progenitor Cells and Macrophages/Microglia Produce Glioma Stem Cell Niches at the Tumor Border

EBioMedicine. 2018 Apr:30:94-104. doi: 10.1016/j.ebiom.2018.02.024. Epub 2018 Mar 1.

Abstract

Glioblastoma (GBM) usually develops in adult brain white matter. Even after complete resection, GBM recurs around the tumor removal cavity, where GBM cells acquire chemo-radioresistance. Characterization of the tumor border microenvironment is critical for improving prognosis in patients with GBM. Here, we compared microRNA (miRNA) expression in samples from the tumor, tumor border, and periphery by miRNA microarray. The top three of miRNAs showing higher expression in the tumor border were related to oligodendrocyte differentiation, and pathologically oligodendrocyte lineage cells were increased in the border, where macrophages and microglia also colocalized. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, similar to that produced by FGF1, EGF and HB-EGF, IL-1β, corresponding to OPCs and macrophages, respectively. Thus, OPCs and macrophages/microglia may form a glioma stem cell niche at the tumor border, representing a promising target for prevention of recurrence.

Keywords: Border niche; Chemoradioresistance; Glioblastoma; Glioma stem cells niche; Macrophage; Microglia; Oligodendrocyte progenitor cell; Recurrence; Stemness; microRNA.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Communication / drug effects
  • Cell Communication / genetics
  • Cell Line, Tumor
  • Cell Lineage / drug effects
  • Cell Survival / drug effects
  • Culture Media, Conditioned / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology*
  • MicroRNAs / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Oligodendrocyte Precursor Cells / drug effects
  • Oligodendrocyte Precursor Cells / metabolism
  • Oligodendrocyte Precursor Cells / pathology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Stem Cell Niche* / drug effects
  • White Matter / pathology

Substances

  • Culture Media, Conditioned
  • MicroRNAs