Dynamic Interactions between Tumor Cells and Brain Microvascular Endothelial Cells in Glioblastoma

SIMPLE SUMMARY: In glioblastoma (GBM), tumor cells develop a symbiotic relation with brain microvascular endothelial cells (BMECs) to shift tissue homeostasis toward a tumor-supporting context. Disentangling the molecular mechanisms that govern this dynamic interaction in the context of GBM represents an exciting challenge for the update of conventional treatment and for the development of novel therapeutic targets for this aggressive and lethal brain tumor. ABSTRACT: GBM is the most aggressive brain tumor among adults. It is characterized by extensive vascularization, and its further growth and recurrence depend on the formation of new blood vessels. In GBM, tumor angiogenesis is a multi-step process involving the proliferation, migration and differentiation of BMECs under the stimulation of specific signals derived from the cancer cells through a wide variety of communication routes. In this review, we discuss the dynamic interaction between BMECs and tumor cells by providing evidence of how tumor cells hijack the BMECs for the formation of new vessels. Tumor cell–BMECs interplay involves multiple routes of communication, including soluble factors, such as chemokines and cytokines, direct cell–cell contact and extracellular vesicles that participate in and fuel this cooperation. We also describe how this interaction is able to modify the BMECs structure, metabolism and physiology in a way that favors tumor growth and invasiveness. Finally, we briefly reviewed the recent advances and the potential future implications of some high-throughput 3D models to better understanding the complexity of BMECs–tumor cell interaction.