Ishida Mitsuaki, Kushima Ryoji, Okabe Hidetoshi
Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan.
Oncol Rep. 2009 Jan;21(1):113-7.
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 a 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.
闭合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、黏附以及细胞旁运输中发挥着关键作用。多种闭合蛋白在不同的上皮细胞中表达，且大多数组织表达多种闭合蛋白。已有报道称多种闭合蛋白在各类人类癌症中表达改变，但它们在直肠高分化内分泌肿瘤（类癌肿瘤）中的表达情况尚未得到研究，而直肠高分化内分泌肿瘤是胃肠道中最常见的内分泌肿瘤。本研究采用免疫组化方法，研究了16例直肠高分化内分泌肿瘤中闭合蛋白-2、-3和-4的表达情况，并将其表达模式与胰腺和肺内分泌肿瘤中的表达模式进行了比较。根据既往报道，胰腺内分泌肿瘤对闭合蛋白-3呈阳性反应，对闭合蛋白-2和-4呈阴性反应，并且大多数肺类癌肿瘤对闭合蛋白-2、-3和-4无免疫反应性。然而，我们的免疫组化研究显示，直肠高分化内分泌肿瘤对闭合蛋白-2、-3和-4呈弥漫性阳性免疫反应。这些结果表明，闭合蛋白的表达取决于内分泌肿瘤的起源部位。此外，直肠高分化内分泌肿瘤中闭合蛋白-3和-4的表达提示了一种新的治疗策略的可能性。闭合蛋白-3和-4是产气荚膜梭菌细胞毒素的受体。这种细胞毒素能快速、特异性地裂解表达闭合蛋白-3和-4的细胞，在癌症治疗中具有潜在应用价值。因此，这种细胞毒素未来可能适用于治疗直肠高分化内分泌肿瘤，以预防肿瘤切除后意外的转移复发，因为这些肿瘤尽管体积较小，但转移发生率相对较高。
