NOS3 and central nervous system cancer: In summary, glioma cells express SP and HK-1 [10,16] and, upon release, SP and HK-1 bind to the NK-1R of glioma vessel endothelial cells, inducing endothelial cell proliferation, migration, adhesion, tube formation, and activation of ERK1/2 phosphorylation leads to stimulation of nitric oxide production and increases in eNOS and VEGF expression which are involved in glioma angiogenesis.