Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions
Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions
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DOI：
10.1080/21688370.2019.1593775
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发表时间：
2019-01-01
期刊：
影响因子：
3.1
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Ueno, Yoshitomo;Ozaki, Saya;Tanaka, Junya
氯离子胞内通道蛋白2（CLIC 2）属于保守的后生动物蛋白CLIC家族。尽管CLIC已被鉴定为氯离子通道，但它们目前被认为是多功能蛋白质。CLIC 2是研究最少的家族成员。我们研究了CLIC 2在人肝细胞癌、肝转移性结直肠癌和结直肠癌中的表达和定位。在人体组织中发现了编码CLIC 1、2、4和5的mRNA的显著表达，但只有CLIC 2主要在癌块周围的非癌组织中表达。纤维化或功能障碍（天冬氨酸转氨酶>= 40）的非癌肝组织和晚期HCC组织表达低水平的CLIC 2。在非癌组织中，衬在血管而不是淋巴管上的内皮细胞表达CLIC 2以及高水平的紧密连接蛋白claudins 1和5、occludin和ZO-1。癌组织中血管内皮细胞CLIC 2和紧密连接蛋白的表达水平较低。从非癌组织分离的CD 31（+）/CD 45（-）内皮细胞表达编码CLIC 2、claudin 1、occludin和ZO-1的mRNA，而来自癌组织的类似细胞组分具有这些分子的非常低的表达。在人脐静脉内皮细胞（HUVEC）中CLIC 2表达的敲低允许人癌细胞穿过HUVEC单层迁移。这些结果表明，CLIC 2可能参与紧密连接的形成和/或维持，并且癌组织脉管系统缺乏CLIC 2和紧密连接，这允许血行转移所必需的癌细胞的内渗。
Chloride intracellular channel protein 2 (CLIC2) belongs to the CLIC family of conserved metazoan proteins. Although CLICs have been identified as chloride channels, they are currently considered multifunctional proteins. CLIC2 is the least studied family member. We investigated CLIC2 expression and localization in human hepatocellular carcinoma, metastatic colorectal cancer in the liver, and colorectal cancer. Significant expression of mRNAs encoding CLIC1, 2, 4, and 5 were found in the human tissues, but only CLIC2 was predominantly expressed in non-cancer tissues surrounding cancer masses. Fibrotic or dysfunctional (aspartate aminotransferase >= 40) non-cancer liver tissues and advanced stage HCC tissues expressed low levels of CLIC2. Endothelial cells lining blood vessels but not lymphatic vessels in non-cancer tissues expressed CLIC2 as well as high levels of the tight junction proteins claudins 1 and 5, occludin, and ZO-1. Most endothelial cells in blood vessels in cancer tissues had very low expressions of CLIC2 and tight junction proteins. CD31(+)/CD45(-) endothelial cells isolated from non-cancer tissues expressed mRNAs encoding CLIC2, claudin 1, occludin and ZO-1, while similar cell fractions from cancer tissues had very low expressions of these molecules. Knockdown of CLIC2 expression in human umbilical vein endothelial cells (HUVECs) allowed human cancer cells to transmigrate through a HUVEC monolayer. These results suggest that CLIC2 may be involved in the formation and/or maintenance of tight junctions and that cancer tissue vasculature lacks CLIC2 and tight junctions, which allows the intravasation of cancer cells necessary for hematogenous metastasis.