The Dual Role of Nitric Oxide in Glioma

Malignant gliomas bear the most dismal prognosis of all human cancers despite the progress in therapy of many other tumors. The search for alternative and complementary treatments has therefore a high priority. Emerging knowledge of the dual and diverging role of nitric oxide in glioma biology has focused on possibilities to achieve anti-glioma effects by modulation of nitric oxide (NO) release and function in these tumors. NO has been shown to influence proliferation of glioma cells, vascular function in glioams, invasive capacity of gliomas, effects of chemo and radiotherapy and also immune reactivity against these tumors. The mechanisms behind the reported diverse and dual effects of NO in glioma biology are multiple. Some of the diversity can be explained by different experimental setups as in vitro versus in vivo models but the cellular sources, timing, absolute levels and gradients play a decisive role for the effects of NO on glioma biology. Current research in this field is hampered by the lack of inhibitors and donors approved for clinical use.