Gliomas are the most common primary brain tumors. However, little is understood about the underlying signaling pathways involved in glioma biology. We are investigating a potential role of nitric oxide (NO) in brain tumor biology in high grade mouse gliomas generated using the RCAS-tva system of somatic cell gene transfer. The activity of endothelial nitric oxide synthase (eNOS), the enzyme which makes nitric oxide, is elevated in gliomas but its functional significance remains unknown. Immunofluorescent analysis of these tumors indicate that eNOS is expressed in endothelial cells in regions of microvascular proliferation (MVP) that constitute the stem cell niche of these tumors. The cells which express the receptor for NO are found in regions of MVP and pseudopalisading zones implying that NO signaling may be regulating the niche in some way. In order to investigate this possibility, we are using bioluminescence and other techniques to measure the effect of NO on signaling pathways that regulate stem cell character such as the sonic hedge (Shh), Wnt and Notch pathways. Preliminary data indicate that NO may influence stem cell characteristics by activating some of these pathways.
