Claudin expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors)
Claudin expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors)
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DOI：
10.3892/or_00000197
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发表时间：
2009-01-01
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：
Ishida, Mitsuaki;Kushima, Ryoji;Okabe, Hidetoshi
紧密连接蛋白是紧密连接的结构和功能成分，在维持细胞极性、细胞排列、粘附和细胞旁转运中起着重要作用。不同的紧密连接蛋白在不同的上皮细胞中表达，并且大多数组织表达多种紧密连接蛋白蛋白。在各种人类癌症中已经报道了claudins表达的改变，但是它们在直肠高分化内分泌肿瘤（类癌肿瘤）（胃肠道中最常见的内分泌肿瘤）中的表达还有待研究。应用免疫组织化学方法对16例直肠高分化内分泌肿瘤中claudins-2、-3和-4的表达进行了研究，并与胰腺和肺内分泌肿瘤中的表达模式进行了比较。大多数肺类癌对claudins-2、claudins-3和claudins-4无免疫反应。然而，我们的免疫组化研究显示，直肠高分化内分泌肿瘤呈弥漫性阳性反应的claudins-2，-3和-4。这些结果表明，claudin的表达依赖于内分泌肿瘤的起源部位。此外，claudin-3和claudin-4在直肠高分化内分泌肿瘤中的表达提示了新的治疗策略的可能性。Claudins-3和Claudins-4是细胞毒性产气荚膜梭菌肠毒素的受体。这种肠毒素快速且特异性地裂解表达紧密连接蛋白-3和紧密连接蛋白-4的细胞，并且在癌症治疗中具有潜在的应用。因此，这种肠毒素可能适用于治疗直肠分化良好的内分泌肿瘤在未来，以防止肿瘤切除术后意外的转移复发，因为这些肿瘤具有相对较高的转移发生率，尽管它们的大小。
Claudins are the structures and functional components of tight junctions and have crucial roles in the maintenance of cell polarity, cellular arrangement, adhesion and paracellular transport. Various claudins are expressed in different epithelial cells and most tissues express multiple claudin proteins. The altered expression of claudins has been reported in various human carcinomas, but their expression in rectal well-differentiated endocrine neoplasms (carcinoid tumors), the most common endocrine tumors in the gastrointestinal tract, has yet to be examined. The expression of claudins-2, -3 and -4 in 16 rectal well-differentiated endocrine neoplasms was studied by immunohistochemical methods, and compared with their expression patterns in endocrine tumors of the pancreas and lung, According to previous reports, pancreatic endocrine tumors were positive for claudin-3 and negative for claudins-2 and -4, and a majority Of lung carcinoid tumors showed no immunoreactivity to claudins-2, -3 and -4. However, our immunohistochemical study revealed that the rectal well-differentiated endocrine neoplasms showed diffuse positive immunoreactivity to claudins-2, -3 and -4. These results indicate that claudin expression depends on the site of origin of endocrine tumors. In addition, claudin-3 and -4 expression in rectal well-differentiated endocrine neoplasms suggests the possibility of new therapeutic strategy. Claudins-3 and -4 are receptors for the cytotoxic Clostridium perfringens enterotoxin. This enterotoxin rapidly and specifically lyses cells expressing claudins-3 and -4 and has a potential application in cancer therapeutics. Accordingly, this enterotoxin may be applicable for the treatment of rectal well-differentiated endocrine neoplasms in the future in order to prevent unexpected metastatic recurrences after tumor resections, because these neoplasms have a relatively high incidence of metastases despite their small size.