System Tumors Expression of Nitric Oxide Synthase in Human Central Nervous

Thenitricoxidesynthases (NOS)area familyof relatedenzymeswhich regulate the production of NO, a free radical gas Implicated in a wide variety of biological processes.Vasodilatlon and increased tumor blood flow, increasedvascularpermeability,modulationof host tumoricidal activity, and free radical injury to tumor cells and adjacent normal tissues are pathophyslological features of malignant tumors that may be medi ated by NO. We examined human brain tumors for three NOS isoforins and NADPH dlaphorase, a histochenaical marker of NOS activity m the brain. We detected increased expression of the brain and endothelial forms of NOS [NOS I and NOS II, respectively (C. Nathan and Q. Xie. Cell, 78: 915—919, 1994)]in astrocytictumors,and the highestlevelsof expressionwasfound in higher grade tumors. Eachof thesetwo isoforms was found In tumor cells and tumor endothelial cells. The macrophage isoform of NOS (NOS ifi) was less frequently detected and expressed at a lowerlevel,predominantlyin tumorendothelial cells.NADPH diaphorase staining for NOS activity paralleled this pattern of NOS expression. Western blot analysis of tumor tissues for these NOS isofonns confirmed these observations. Our data indicate that malignant central nervous system neoplasms express unexpectedly high levels of NOS and suggest that NO production may be associated with pathophyslological processes important to these tumors.