Histological Characterization of the Tumorigenic “Peri-Necrotic Niche” Harboring Quiescent Stem-Like Tumor Cells in Glioblastoma
Fig 7
A schematic model illustrating the main findings of this study.
The SOX2+ (or NANOG+) HIF-1α+ RNApII-S2P-/low cells identified in this study represent hypoxic quiescent stem-like tumor cells, and the emergence of these cells is associated with an increased sphere-forming activity. Thus, the most common locations of these cells, namely, the neighborhood of large ischemic necroses in glioblastoma tissues (“peri-necrotic niche”) and the zone of intermediate depth from the surface of the spheroids cultured under 5% O2, indicate a microenvironment supporting tumorigenicity. Since a gradient of O2 concentration is present within the glioblastoma tissues and spheroids, this microenvironment is formed under an appropriate level of hypoxia.