Contribution of the Microenvironmental Niche to Glioblastoma Heterogeneity

Figure 1

Tumor microenvironment and its effect on GSCs. Dialogues between tumor cells and other cell types in the microenvironment create vascular niches that regulate tumor growth. The perivascular niche contains cells such as ECs, pericytes, astrocytes, macrophages, and microglial. Each component of the perivascular niche interacts with GSCs to promote glioma cells growth and proliferation, maintain GSCs stemness, and control vascular integrity. GBM contains areas of pseudopalisading necrosis that is the core of the hypoxic niche. Hypoxia upregulates HIFs that induce the expression of oncogenes and transcription factors such as c-Myc and STAT3 involved in stem cells maintenance and expansion. Hypoxia also contributes to metabolic programming and recruitment of macrophages and microglial. These cells form the inflammatory niche, where TAMs secrete soluble factors such as TGF-β and IL-6 that expand GSCs population and promote glioma invasion. Interaction between GSCs and the various players in the microenvironment orchestrate tumor cells responds to therapeutic interventions, thus contributing to the heterogeneity of the tumor.