Tokuhara Yasunori, Morinishi Tatsuya, Matsunaga Toru, Sakai Manabu, Sakai Takayoshi, Ohsaki Hiroyuki, Kadota Kyuichi, Kushida Yoshio, Haba Reiji, Hirakawa Eiichiro
Laboratory of Pathology, Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa 761-0123, Japan.
Department of Medical Technology, Ehime Prefectural University of Health Sciences, Tobe, Ehime 791-2101, Japan.
Oncol Lett. 2018 Jan;15(1):99-108. doi: 10.3892/ol.2017.7281. Epub 2017 Oct 26.
Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well- to moderately-differentiated colorectal adenocarcinomas (P<0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in detail, the present results indicated the potential of claudin-3 as a histopathological biomarker for colorectal adenocarcinomas.
闭合蛋白是一个跨膜蛋白大家族的成员，对紧密连接的形成至关重要，并对肿瘤进展的生物学行为有显著影响。先前的研究表明，几种闭合蛋白在多种癌症类型中呈现异常表达模式。本研究调查了闭合蛋白-3和闭合蛋白-7在人结肠直肠腺癌细胞系和组织中的表达及定位。采用免疫细胞化学和免疫组织化学染色法测定闭合蛋白-3和闭合蛋白-7的蛋白表达水平。在人结肠直肠腺癌Caco-2和SW620细胞系中，闭合蛋白-3呈现核定位，而闭合蛋白-7未呈现。获取手术切除的结肠直肠腺癌组织标本，分析闭合蛋白-3或闭合蛋白-7的表达与各种临床病理参数之间的关联。闭合蛋白-3和闭合蛋白-7的膜表达率分别为58.0%和50.0%，而它们的核表达率分别为22.0%和2.0%。闭合蛋白-3和闭合蛋白-7的膜表达与任何临床病理因素均无关联，而闭合蛋白-3的核表达与组织学类型相关，与高分化至中分化结肠直肠腺癌相比，在结肠直肠黏液腺癌中显著升高（P<0.01）。然而，未观察到闭合蛋白-7的核表达与任何临床病理参数之间存在关联。总之，结肠直肠黏液腺癌中闭合蛋白-3的核表达可能参与肿瘤的生物学转变。本研究结果表明，闭合蛋白-3是一种与组织学类型相关的重要蛋白，具有作为预后标志物的潜力。尽管闭合蛋白-3在肿瘤发生过程中核定位的潜在机制尚未详细阐明，但本研究结果表明闭合蛋白-3作为结肠直肠腺癌组织病理学生物标志物的潜力。
