The expression of nitric oxide synthases in human brain tumours and peritumoral areas
The expression of nitric oxide synthases in human brain tumours and peritumoral areas
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DOI：
10.1016/s0022-510x(97)00315-8
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发表时间：
1998-03-05
影响因子：
4.4
通讯作者：
Sarkar, C
中科院分区：
文献类型：
--
作者：
Bakshi, A;Nag, TC;Sarkar, C
一氧化氮是一种有效的信号分子，由一氧化氮合酶 (NOS) 从 L-精氨酸产生，与多种病理生理过程有关。恶性肿瘤的许多特征，例如血管通透性增加、血管舒张、新血管形成以及对肿瘤和邻近正常组织的自由基损伤被认为是由一氧化氮介导的。虽然 NOS 表达已在脑部谣言中得到证实，但尚未有关于邻近瘤周脑区的同等研究报道。本研究检查了人类肿瘤和瘤周脑区域中 NOS 的表达模式。对八名患者（六名神经胶质瘤、脑膜瘤和转移性腺癌各一名）进行了活检，这些患者来自三个区域：肿瘤、瘤周和明显“正常”的邻近脑组织。对三种 NOS 亚型进行免疫组织化学染色：脑 NOS (BNOS)、内皮 NOS (ENOS) 和巨噬细胞特异性 NOS (MacNOS)。除多形性胶质母细胞瘤和转移性腺癌外，肿瘤细胞表达所有三种 NOS 亚型。在四种肿瘤中，ENOS 表达存在明显的梯度，远离肿瘤。在三个神经胶质瘤中，许多神经胶质细胞被 BNOS 强烈标记。这种标记在瘤周组织中减少。在四种肿瘤中，血管内和周围的细胞（可能是淋巴细胞和 CD 45 阳性巨噬细胞）被 MacNOS 强烈标记。这些结果表明一氧化氮是在肿瘤细胞和肿瘤血管内皮细胞中产生的，而偶尔神经胶质细胞也可能被诱导产生一氧化氮。讨论了一氧化氮在瘤周水肿产生中的可能作用。 (C) 1998 Elsevier Science B.V.
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 rumours, 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. (C) 1998 Elsevier Science B.V.