Angiogenesis in gliomas

Malignant brain tumors, including glioblastoma (GBM), display growth, survival, and invasive properties that are coupled to blood vessels and vascular-derived factors. For example, GBM stem cells (GSCs) home to perivascular niches and invasive tumor cells commonly disperse through the brain microenvironment via extracellular matrix (ECM)-rich vascular basement membranes. Anti-vascular agents that target angiogenesis, and particularly those involving vascular endothelial cell growth factor-A (VEGF-A) and its receptors, improve progression-free survival in GBM patients. However, these benefits are often transient due to compensation by alternative angiogenic pathways. The detailed molecular mechanisms that couple GBM cells to blood vessels during tumor growth and progression as well as following anti-angiogenesis therapies are just beginning to be elucidated, with various cytokines, growth factors, and ECM proteins playing important roles. In this review we will highlight molecular pathways that link cerebral blood vessels and GBM cells during tumor growth, progression, and invasion. We will also discuss mechanisms underlying GBM-induced angiogenesis, with a particular focus placed on roles for integrin adhesion receptors and their ECM protein ligands. Therapies that target angiogenesis in GBM and other brain cancers will also be summarized.