Patients with brain tumours have a range of symptoms that can vary in severity, from headaches to a decline in cognitive function. The symptoms depend on the tumour type and its size, location and growth rate. Understanding what controls the growth rate of brain tumours might therefore lead to the development of therapies that slow cancer progression and improve the quality of life of people who have this type of cancer. In this report, Venkataramani and colleagues show that cancer cells form excitatory synaptic connections with neurons in the central nervous system. This connection accelerates tumour growth rate and lethality. Specifically, these neurogliomal synapses show a typical synaptic ultrastructure, are located on tumour “microtubes”, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype. Tumour invasion and growth were reduced by anaesthesia and the AMPA receptor antagonist perampanel, respectively. These findings reveal a biologically relevant direct synaptic communication between neurons and glioma cells with potential clinical implications.
Venkataramani V, Tanev DI, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T, Körber C, Kardorff M, Ratliff M, Xie R, Horstmann H, Messer M, Paik SP, Knabbe J, Sahm F, Kurz FT, Acikgöz AA, Herrmannsdörfer F, Agarwal A, Bergles DE, Chalmers A, Miletic H, Turcan S, Mawrin C, Hänggi D, Liu HK, Wick W, Winkler F, Kuner T: Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 573(7775):532-538 (2019).