The expression of nitric oxide synthases in human brain tumours and peritumoral areas

Nitric oxide, a potent signalling molecule produced from L-arginine by nitric oxide synthase (NOS), has been implicated in diverse pathophysiological processes. Many characteristics of malignant tumours such as increased vascular permeability, vasodilation, neovascularisation and free radical injury to the tumour and adjacent normal tissues are believed to be mediated by nitric oxide. While NOS expression has been demonstrated in brain tumours, no equivalent studies have yet been reported on the adjacent peritumoral brain region. The present study examined the pattern of NOS expression in the human tumour and peritumoral brain areas. Biopsies were obtained from eight patients (six gliomas, one each of meningioma and metastatic adenocarcinoma) from three areas: tumour, peritumoral, and apparently 'normal' adjacent brain tissue. Immunohistochemical staining was performed for three isoforms of NOS: brain NOS (BNOS), endothelial NOS (ENOS) and macrophage-specific NOS (MacNOS). Except for glioblastoma multiforme and metastatic adenocarcinoma, the tumour cells expressed all three NOS isoforms. In four tumours, there was a demonstrable gradient of ENOS expression falling away from the tumour. In three gliomas, many glial cells were intensely labelled with BNOS. This labelling decreased in the peritumoral tissues. In four tumours, cells (presumably lymphocytes, and CD 45 positive macrophages) were labelled intensely with MacNOS in and around the blood vessels. These results suggest that nitric oxide is produced in the tumour cells and endothelium of tumour vasculature, while occasionally glial cells may also be induced to produce it. The possible role of nitric oxide in the production of peritumoral oedema is discussed.