Figure 2.

Illustration of the complex cellular and non-cellular ECM interactions in the glioma tumor microenvironment. The normal brain’s ECM differs from that of other organs because it contains very little of the fibrotic ECM proteins collagen, fibronectin, and laminin. On the other hand, the brain parenchyma is abundant in proteoglycans, connecting proteins, and glycosaminoglycans (hyaluronic acid). The ECM is transformed in GBM tumors compared to healthy brain tissue, and it is crucial for tumor invasion and migration. The ECM of GBM contains higher levels of collagen, fibronectin, laminin, hyaluronic acid, tenascin C, and vitronectin, all of which have been linked to glioma growth, invasion, and chemo- and radio-resistance. Due to the complex interactions between glioma cells and the non-cellular components in the GBM TME, targeting the ECM directly and attempting to alter the tumor production of ECM proteins, and thereby reduce tumor growth, should improve the infiltration of immune cells, drugs and provide improved therapies for highly malignant brain tumors. [Created with BioRender.com].