EXPRESSION OF NITRIC-OXIDE SYNTHASE IN HUMAN CENTRAL-NERVOUS-SYSTEM TUMORS

The nitric oxide synthases (NOS) are a family of related enzymes which regulate the production of NO, a free radical gas implicated in a wid e variety of biological processes. Vasodilation and increased tumor bl ood flow, increased vascular permeability, modulation of host tumorici dal activity, and free radical injury to tumor cells and adjacent norm al tissues are pathophysiological features of malignant tumors that ma y be mediated by NO. We examined human brain tumors for three NOS isof orms and NADPH diaphorase, a histochemical marker of NOS activity in t he brain. We detected increased expression of the brain and endothelia l forms of NOS [NOS I and NOS II, respectively (C. Nathan and Q. Xie. Cell, 78: 915-919, 1994)] in astrocytic tumors, and the highest levels of expression was found in higher grade tumors. Each of these two iso forms was found in tumor cells and tumor endothelial cells. The macrop hage isoform of NOS (NOS LU) was less frequently detected and expresse d at a lower level, predominantly in tumor endothelial cell. NADPH dia phorase staining for NOS activity paralleled this pattern of NOS expre ssion. Western blot analysis of tumor tissues for these NOS isoforms c onfirmed these observations. Our data indicate that malignant central nervous system neoplasms express unexpectedly high levels of NOS and s uggest that NO production may be associated with pathophysiological pr ocesses important to these tumors.