FIG. 3.

The invasive niche in GBM. The invasive niche is characterized by proliferating microvasculature that breaks down the ECM and invades the surrounding healthy brain tissue, beyond the area of the tumor. Major cell types, such as glioma cells, GSCs, GdECs, ECs, pericytes, microglia, and reactive astrocytes, reside in invasive niches. An invasive niche is formed by GSC differentiation into GdECs, which stimulates host EC recruitment via WNT5A to create a vascular-like niche, thereby promoting tumor cell growth beyond the primary tumor microenvironment. Manipulating niche-relevant cell types could be a therapeutic strategy. For instance, amphotericin B, an antifungal drug, shows inhibition of tumor progression by reducing glioma-associated microglia. EC, endothelial cell; ECM, extracellular matrix; GdEC, GSC-derived endothelial-like cell.