Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
PLoS One. 2013 Sep 20;8(9):e74757. doi: 10.1371/journal.pone.0074757. eCollection 2013.
Claudins are known as tight junction proteins, and their expression pattern in gastric cancer is still controversial. The relationship between the expression patterns of tight junction proteins and tumor proliferation in early gastric cancer is still far from clear.
To investigate the expression patterns of claudin-18 and Ki-67 in early gastric cancer at the invasive front and surrounding normal gastric mucosa and to investigate the biological function of claudin-18 in the proliferation and invasion of cancer cells.
Seventy-five early gastric cancer lesions removed via endoscopic mucosal resection or endoscopic submucosal resection were evaluated. All gastric cancer lesions were diagnosed as differentiated adenocarcinoma using the Japanese Classification of Gastric Carcinoma. To assess epithelial proliferation, immunostaining with Ki-67 was performed, and the labeling index was calculated. To assess the expression of epithelial tight junction proteins, immunofluorescent staining of claudin-18 was performed. The immunoreactivity of claudin-18 was graded according to the number of stained cells. Correlation analysis was performed by Spearman's rank correlation coefficient. Transfection of claudin-18 small interfering RNA (siRNA) was accomplished in MKN74, a claudin-18-positive gastric cancer cell line, to investigate the effect of claudin-18 on proliferation and invasion of cancer cells.
Claudin-18 was significantly down-regulated in gastric cancer compared to surrounding gastric normal mucosa or intestinal metaplasia. The Ki-67 labeling index of gastric cancer at the invasive front was inversely correlated with the claudin-18 level, but that at the mucosal lesion was not correlated. Claudin-18 knockdown significantly promoted the proliferation of MKN74 compared with control siRNA-transfected cells. MKN74 invasion increased significantly with claudin-18 siRNA transfection compared with control siRNA transfection.
Down-regulation of claudin-18 is associated with the proliferative potential at the invasive front of gastric cancer, suggesting that it has a pivotal role in gastric cancer progression.
紧密连接蛋白 Claudin 家族的表达模式在胃癌中仍存在争议。紧密连接蛋白表达模式与早期胃癌肿瘤增殖之间的关系仍不清楚。
研究 Claudin-18 和 Ki-67 在早期胃癌侵袭前沿和周围正常胃黏膜中的表达模式，并探讨 Claudin-18 在癌细胞增殖和侵袭中的生物学功能。
对 75 例经内镜黏膜切除术或内镜黏膜下剥离术切除的早期胃癌病变进行评估。所有胃癌病变均采用日本胃癌分类法诊断为分化型腺癌。为评估上皮细胞增殖，进行 Ki-67 免疫组化染色，并计算标记指数。为评估上皮紧密连接蛋白的表达，进行 Claudin-18 的免疫荧光染色。根据染色细胞数对 Claudin-18 的免疫反应性进行分级。采用 Spearman 秩相关系数进行相关性分析。在 Claudin-18 阳性胃癌细胞系 MKN74 中转染 Claudin-18 小干扰 RNA（siRNA），以研究 Claudin-18 对癌细胞增殖和侵袭的影响。
与周围正常胃黏膜或肠上皮化生相比，Claudin-18 在胃癌中明显下调。胃癌侵袭前沿的 Ki-67 标记指数与 Claudin-18 水平呈负相关，但黏膜病变处无相关性。与对照 siRNA 转染的细胞相比，Claudin-18 下调显著促进了 MKN74 的增殖。与对照 siRNA 转染相比，MKN74 的侵袭能力在 Claudin-18 siRNA 转染后显著增加。
Claudin-18 的下调与胃癌侵袭前沿的增殖潜能相关，提示其在胃癌进展中具有关键作用。
