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

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.
Highlights • Most cases of glioblastoma recur in white matter around the removal cavity after total resection plus chemo-radiotherapy. • miRNAs showing characteristically higher expression in the tumor border were related to oligodendrocyte differentiation. • Increased oligodendrocyte progenitor cells and macrophages enhance stemness and chemo-radioresistance in glioma cells. Glioblastoma (GBM) occurs in adult brain and shows rapid growth and invasion. Despite intensive treatment, the mean 5-year survival rate is still