Intrinsic protective mechanisms of the neuron-glia network against glioma invasion

•The normal neuron-glia network of the brain has many molecules that inhibit cellular invasion, including that of glioma.•Radiation therapy may injure the innate inhibitory mechanisms favoring tumor invasion.•To understand the interaction between glioma cells and the surrounding neuron-glia network is crucial for developing new therapies.

Gliomas arising in the brain parenchyma infiltrate into the surrounding brain and break down established complex neuron-glia networks. However, mounting evidence suggests that initially the network microenvironment of the adult central nervous system (CNS) is innately non-permissive to glioma cell invasion. The main players are inhibitory molecules in CNS myelin, as well as proteoglycans associated with astrocytes. Neural stem cells, and neurons themselves, possess inhibitory functions against neighboring tumor cells. These mechanisms have evolved to protect the established neuron-glia network, which is necessary for brain function. Greater insight into the interaction between glioma cells and the surrounding neuron-glia network is crucial for developing new therapies for treating these devastating tumors while preserving the important and complex neural functions of patients.