Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue
Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue
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DOI：
10.1369/jhc.4a6606.2005
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发表时间：
2005-09-01
影响因子：
3.2
通讯作者：
Obeid, LM
中科院分区：
文献类型：
--
作者：
Johnson, KR;Johnson, KY;Obeid, LM
鞘氨醇激酶 1 (SK1) 是鞘脂代谢途径的关键酶，负责催化生物活性脂质 1-磷酸鞘氨醇的形成。 SK1 介导的 1-磷酸鞘氨醇的产生已被证明可以刺激细胞生长、分化、迁移、血管生成和细胞凋亡抑制等生物过程。在这项研究中，在肺的支气管/终末细支气管中检查了 SK1 的细胞类型特异性免疫定位。支气管假复层上皮细胞顶面和下面的平滑肌细胞、粘膜下浆液腺、未成熟软骨细胞、11型肺泡细胞、泡沫巨噬细胞、血管内皮细胞和神经束有明显的强免疫阳性染色。对 25 个正常/肿瘤患者匹配的非小细胞肺癌组织样本进行 SK1 表达的免疫组织化学筛查，发现 25 个肿瘤样本中的 25 个（类癌 [5 个样本]、鳞状细胞 [10 个样本] 和腺癌 [10 个样本]）与患者匹配的正常组织相比，表现出压倒性的 SK1 免疫染色阳性。此外，与正常组织以及其他几种实体瘤相比，在肺癌组织中观察到 SK1 mRNA 表达升高约 2 倍。总而言之，这些发现定义了 SK1 在肺中的定位，并为 SK1 如何在正常肺生理学和肺癌病理生理学中发挥作用提供了线索。
Sphingosine kinase 1 (SK1) is a key enzyme critical to the sphingolipid metabolic pathway responsible for catalyzing the formation of the bioactive lipid sphingosine-1-phosphate. SK1-mediated production of sphingosine-1-phosphate has been shown to stimulate such biological processes as cell growth, differentiation, migration, angiogenesis, and inhibition of apoptosis. In this study, cell type-specific immunolocalization of SK1 was examined in the bronchus/terminal bronchiole of the lung. Strong immunopositive staining was evident at the apical surface of pseudostratified epithelial cells of the bronchus and underlying smooth muscle cells, submucosal serous glands, immature chondrocytes, type 11 alveolar cells, foamy macrophages, endothelial cells of blood vessels, and neural bundles. Immunohistochemical screening for SK1 expression was performed in 25 samples of normal/tumor patient matched non-small-cell lung cancer tissue and found that 25 of 25 tumor samples (carcinoid [5 samples], squamous [10 samples], and adenocarcinoma tumors [10 samples]), exhibited overwhelmingly positive immunostaining for SK1 as compared with patient-matched normal tissue. In addition, an approximately 2-fold elevation of SK1 mRNA expression was observed in lung cancer tissue versus normal tissue, as well as in several other solid tumors. Taken together, these findings define the localization of SK1 in lung and provide clues as to how SK1 may play a role in normal lung physiology and the pathophysiology of lung cancer.