Is There a Role for Nitric Oxide in Tumor Angiogenesis?

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Abstract
In this issue of the Journal, Gallo et al. (1) report an interesting analysis of nitric oxide production and angiogenesis in head and neck cancers. They observed the following: 1) Tumor levels of total nitric oxide synthase activity (including inducible nitric oxide synthase activity) and of 38,58 cyclic guanosine monophosphate (cGMP) (a known mediator of cellular response to nitric oxide) were statistically significantly higher than those found in normal mucosa; 2) tumor specimens from patients with cervical lymph node metastases were more angiogenic (i.e., they had greater microvessel density) than specimens of nonmetastatic tumors; 3) when tumor specimens with high levels of nitric oxide synthase were implanted in the rabbit cornea, angiogenesis was induced, but this angiogenesis was suppressible by inhibitors of nitric oxide synthesis; and 4) angiogenesis at the tumor edge was an independent predictor of metastasis, a finding that is consistent with previous reports [see(2)] of patients with other types of cancer. These results reveal a strong positive correlation between the expression of nitric oxide synthase and tumor angiogenesis and tumor progression.
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