Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma
Claudin expression profiles in Epstein-Barr virus-associated nasopharyngeal carcinoma
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DOI：
10.3892/or_00000716
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发表时间：
2010-04-01
期刊：
影响因子：
4.2
通讯作者：
Okabe, Hidetoshi
中科院分区：
文献类型：
--
作者：
Kojima, Fumiyoshi;Ishida, Mitsuaki;Okabe, Hidetoshi
紧密连接蛋白（Claudin）是紧密连接的结构和功能组分，在维持细胞排列、粘附和细胞旁转运中起着重要作用。最近的研究表明，claudin表达的变化和/或缺失在肿瘤发生和肿瘤进展中起重要作用，并且在各种人类癌症中已经报道了Claudius的表达改变。非角化性鼻咽癌（Non-keratinizing nasopharyngeal carcinoma，NPC）是一种常见的EB病毒（Epstein-Barr Virus，EBV）相关性鼻咽癌，具有独特的临床病理特征。本研究的目的是调查密封蛋白在EBV相关的非角化型NPC中的表达谱。采用免疫组化方法检测18例EB病毒相关非角化型鼻咽癌中claudin-1、claudin-2、claudin-3、claudin-4的表达。Claudin-1在所有18例中表达，而claudin-2在所有18例中均不表达。Claudin-3表达是可变的，18例中有8例（45%）显示claudin-3无免疫反应性。Claudin-4在所有病例中显示阳性免疫反应性，即使在Claudin-3阴性的病例中也是如此。紧密连接蛋白-3和紧密连接蛋白-4是细胞毒性产气荚膜梭菌肠毒素（CPE）的受体，并且CPE已经成为表达紧密连接蛋白-3和/或紧密连接蛋白-4的恶性肿瘤的潜在治疗靶标，因为CPE特异性地且快速地裂解表达这些蛋白质的细胞。在临床上，EB病毒相关的非角化型鼻咽癌的远处转移治疗是一个严重的问题，因为在发现原发肿瘤之前，经常会有淋巴结转移和远处转移，因此CPE治疗可能是EB病毒相关的非角化型鼻咽癌的一个潜在的治疗靶点，因为我们的研究结果清楚地显示了claudin-3和/或claudin-4在所有研究病例中的表达。
Claudins are a family of proteins that are structural and Functional components of tight junctions and have crucial roles ill the maintenance Of cellular arrangement, adhesion and paracellular transport. Recent studies have shown that changes and/or loss of claudin expression plays an important role in tumorigenesis and tumor progression, and altered expression Of Claudius has been reported in various human carcinomas. Non-keratinizing nasopharyngeal carcinoma (NPC) is a common Epstein-Barr Virus (EBV)-associated carcinoma with characteristic clinicopathological features. The aim of this study was to investigate claudin expression profiles in EBV-associated non-keratinizing NPC. We analyzed expressions of claudin-1, -2, -3, and -4 in 18 cases of EBV-associated non-keratinizing NPC by immunohistochemical methods. Claudin-1 was expressed in all 18 cases, but claudin-2 was not expressed in any of the 18 cases. Claudin-3 expression was variable, with 8 of the 18 cases (45%) showing no immunoreactivity for claudin-3. Claudin-4 displayed positive immunoreactivity in all cases, even in claudin-3-negative cases. Claudin-3 and -4 are receptors for cytotoxic Clostridium perfringens enterotoxin (CPE) and CPE has emerged as a potential therapeutic target for malignant tumors expressing claudin-3 and/or -4, because CPE specifically and rapidly lyses cells expressing these proteins. Clinically, treatment of distant metastases is a serious problem ill EBV-associated non-keratinizing NPC, because frequently there is lymph node involvement and distant metastasis before detection of the primary tumor.Therefore, CPE therapy may be a potential therapeutic target for EBV-associated non-keratinizing NPC, since our results clearly showed claudin-3 and/or -4 expression in all cases studied.