Glioblastoma: Defining Tumor Niches

Glioblastomas (glioblastoma multiforme, GBM) are one of the most recalcitrant brain tumors because of their aggressive invasive growth and resistance to therapy. They are highly heterogeneous malignancies at both the molecular and histological levels. Specific histological hallmarks including pseudopalisading necrosis and microvascular proliferation distinguish GBM from lower-grade gliomas, and make GBM one of the most hypoxic as well as angiogenic tumors. These microanatomical compartments present specific niches within the tumor microenvironment that regulate metabolic needs, immune surveillance, survival, and invasion, as well as cancer stem cell (CSC) maintenance. We review here the features and functions of the distinct GBM niches, detail the different cell constituents and the functional status of the vasculature, and discuss prospects of therapeutically targeting GBM niche constituents.