Novel concept of the border niche: glioblastoma cells use oligodendrocytes progenitor cells (GAOs) and microglia to acquire stem cell-like features.

Abstract

Glioblastoma (GBM) is a major malignant brain tumor developing in adult brain white matter, characterized by rapid growth and invasion. GBM cells spread into the contralateral hemisphere, even during early tumor development. However, after complete resection of tumor mass, GBM commonly recurs around the tumor removal cavity, suggesting that a microenvironment at the tumor border provides chemo-radioresistance to GBM cells. Thus, clarification of the tumor border microenvironment is critical for improving prognosis in GBM patients. MicroRNA (miRNA) expression in samples from the tumor, tumor border, and peripheral region far from tumor mass was compared, and five miRNAs showing characteristically higher expression in the tumor border were identified, with the top three related to oligodendrocyte differentiation. Pathologically, oligodendrocyte lineage cells increased in the border, but were rare in tumors. Macrophages/microglia also colocalized in the border area. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, suggesting that OPCs and macrophages/microglia constitute a special microenvironment for GBM cells at the tumor border. The supportive function of OPCs for GBM cells has not been discussed previously. OPCs are indispensable for GBM cells to establish special niches for chemo-radioresistance outside the tumor mass.