Oligodendrocyte progenitor cells and macrophages/microglia produce glioma stem cell niche at the tumor border

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 peripheral region far from tumor mass 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 numbers of macrophages and microglia also colocalized. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells. Thus, OPCs and macrophages/microglia may form a glioma stem cell niche at the tumor border, representing a novel promising target for prevention of recurrence. Tissues at three sites, tumor, border area, and peripheral area, were obtained from 12 GBM patients. Upregulated miRNAs in the border region were defined as having more than two-fold higher expression than those in the tumor and periphery; downregulated miRNAs in the border region were defined as having less than half of the expression observed in the tumor and periphery.