Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, Japan.
Anticancer Res. 2012 Jun;32(6):2309-14.
The molecular and morphological alterations of the tight junctions in hepatic metastatic lesions are poorly understood. The possible involvement of claudin-1 (CL-1), which is one of the major tight junctional proteins, was investigated in the tumorigenesis of hepatic metastasis in patients with colorectal cancer (CRC).
A total of 14 patients with hepatic metastasis of CRC who underwent surgical treatment from January 2007 until December 2010 at the Kurume University Hospital in Fukuoka, were examined. CRC tissue specimens were analyzed to determine whether the levels of CL-1 correlated with clinicopathological factors and to determine the roles of CL-1, β-catenin, and E-cadherin in the alterations of the tight junctions during tumorigenesis.
In seven cases, the tumors were located in the colon, while the other seven tumors were found in the rectum. There were eight cases of synchronous liver metastasis, while there were six cases of metachronous liver metastasis. The levels of the CL-1 protein were up-regulated in CRC and in hepatic metastatic lesions. The levels of β-catenin were positive or up-regulated in the primary CRC lesions and in hepatic metastatic lesions. Despite the finding that the levels of E-cadherin were decreased in CRC, they were clearly up-regulated in hepatic metastatic lesions in this study.
This study demonstrated that CL-1 levels were up-regulated in liver metastatic lesions from primary CRC lesions. Moreover, the levels of E-cadherin were increased in liver metastatic lesions, which may point to the existence of interactions between CL-1 and E-cadherin in hepatic metastatic lesions. These observations suggest that CL-1 plays a pivotal role in the regulation of cellular morphology and in the behavior of metastatic processes in CRC.
肝转移瘤中紧密连接的分子和形态改变知之甚少。本研究调查了结蛋白（CL-1）在结直肠癌（CRC）肝转移肿瘤发生中的可能作用，CL-1 是主要的紧密连接蛋白之一。
本研究共纳入了 2007 年 1 月至 2010 年 12 月在福冈久留米大学医院接受手术治疗的 14 例 CRC 肝转移患者。分析 CRC 组织标本，以确定 CL-1 水平是否与临床病理因素相关，并确定 CL-1、β-连环蛋白和 E-钙黏蛋白在肿瘤发生过程中紧密连接改变中的作用。
7 例肿瘤位于结肠，7 例位于直肠。8 例为同时性肝转移，6 例为异时性肝转移。CRC 和肝转移瘤中 CL-1 蛋白水平上调。原发性 CRC 病变和肝转移病变中β-连环蛋白呈阳性或上调。尽管本研究发现 CRC 中 E-钙黏蛋白水平降低，但在肝转移瘤中明显上调。
本研究表明 CL-1 水平在原发性 CRC 肝转移瘤中上调。此外，E-钙黏蛋白在肝转移瘤中上调，这可能表明 CL-1 和 E-钙黏蛋白在肝转移瘤中存在相互作用。这些观察结果表明，CL-1 在 CRC 细胞形态调节和转移过程行为中发挥关键作用。
