Down-regulation of claudin-18 is associated with the proliferative and invasive potential of gastric cancer at the invasive front.
Down-regulation of claudin-18 is associated with the proliferative and invasive potential of gastric cancer at the invasive front.
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DOI：
10.1371/journal.pone.0074757
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Miwa H
中科院分区：
文献类型：
--
作者：
Oshima T;Shan J;Okugawa T;Chen X;Hori K;Tomita T;Fukui H;Watari J;Miwa H
紧密连接蛋白是紧密连接蛋白，其在胃癌中的表达模式仍有争议。早期胃癌中紧密连接蛋白的表达模式与肿瘤增殖的关系尚不清楚。探讨claudin-18和Ki-67在早期胃癌浸润前沿及癌旁正常胃粘膜中的表达规律，探讨claudin-18在癌细胞增殖和侵袭中的生物学作用。75例早期胃癌病变通过内镜粘膜切除术或内镜粘膜下切除术进行了评价。所有胃癌病变均采用日本胃癌分类法诊断为分化腺癌。为了评估上皮增殖，进行Ki-67免疫染色，并计算标记指数。为了评估上皮紧密连接蛋白的表达，进行紧密连接蛋白-18的免疫荧光染色。claudin-18的免疫反应性根据染色细胞的数量进行分级。采用斯皮尔曼等级相关系数进行相关分析。将claudin-18小干扰RNA（siRNA）转染claudin-18阳性的胃癌细胞系MKN 74，研究claudin-18对胃癌细胞增殖和侵袭的影响。Claudin-18在胃癌组织中表达较癌旁正常胃粘膜或肠上皮化生组织明显下调。浸润前沿胃癌组织中Ki-67标记指数与claudin-18水平呈负相关，而黏膜病变组织中Ki-67标记指数与claudin-18水平无相关性。与对照siRNA转染细胞相比，Claudin-18敲低显著促进MKN 74的增殖。与对照siRNA转染相比，用claudin-18 siRNA转染的MKN 74侵袭显著增加。claudin-18的下调与胃癌浸润前沿的增殖潜力相关，表明其在胃癌进展中具有关键作用。
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.
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影响因子：
3.7
作者：
Agarwal R;Mori Y;Cheng Y;Jin Z;Olaru AV;Hamilton JP;David S;Selaru FM;Yang J;Abraham JM;Montgomery E;Morin PJ;Meltzer SJ
通讯作者：
Meltzer SJ
DOI：
10.1007/pl00011720
发表时间：
2000-12-01
期刊：
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
影响因子：
--
作者：
Gotoda, Takuji;Yanagisawa, Akio;Kato, Yo
通讯作者：
Kato, Yo
按地点划分的全球和区域癌症死亡率和发病率估计：II。 2000 年全球疾病负担的结果。
影响因子：
3.8
作者：
Shibuya, K;Mathers, CD;Boschi-Pinto, C;Lopez, AD;Murray, CJL
通讯作者：
Murray, CJL
紧密连接链内和之间异质claudin物种相互作用的方式。
影响因子：
7.8
作者：
Furuse, M;Sasaki, H;Tsukita, S
通讯作者：
Tsukita, S
影响因子：
3.8
作者：
Hewitt, Kyle J.;Agarwal, Rachana;Morin, Patrice J.
通讯作者：
Morin, Patrice J.