Aberrant expression of Cx43 is associated with the peritoneal metastasis of gastric cancer and Cx43-mediated gap junction enhances gastric cancer cell diapedesis from peritoneal mesothelium.
Aberrant expression of Cx43 is associated with the peritoneal metastasis of gastric cancer and Cx43-mediated gap junction enhances gastric cancer cell diapedesis from peritoneal mesothelium.
复制标题
Cx43 的异常表达与胃癌的腹膜转移有关，Cx43 介导的间隙连接增强胃癌细胞腹膜间皮的渗出
DOI：
10.1371/journal.pone.0074527
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Luo HX
中科院分区：
文献类型：
--
作者：
Tang B;Peng ZH;Yu PW;Yu G;Qian F;Zeng DZ;Zhao YL;Shi Y;Hao YX;Luo HX
腹膜转移的过程涉及腹内脱落的胃癌细胞通过间皮细胞单层脱出，但其相关的分子机制尚不清楚。胃癌细胞与间皮细胞间的细胞间隙连接通讯(GJIC)可能在细胞分化过程中发挥积极作用。在这项研究中，我们检测了连接蛋白43(Cx43)在原发胃癌组织、腹内脱落癌细胞和配对的腹膜转移组织中的表达。我们发现Cx43在原发胃癌组织中的表达明显降低；腹内脱落癌细胞和配对的转移腹膜组织与原发胃癌组织相比表达增强。BGC-823和SGC-7901人胃癌细胞表达Cx43或Cx43T154A(一种仅连接缝隙连接但不提供细胞间通讯的突变蛋白)，并与人腹膜间皮细胞(HPMC)共同培养。研究了基质涂层盖片上HPMC单层的异质细胞GJIC和突触作用。我们发现，表达Cx43的BGC-823和SGC-7901胃癌细胞在1小时内与HPMC单层形成功能异细胞缝隙连接。与Cx43T154A和对照组细胞相比，表达Cx43的工程化细胞的滞育显著增加，这表明在表达Cx43的细胞中观察到的滞育上调需要异源细胞GJIC。进一步的研究表明，胃癌细胞通过细胞旁途径通过间皮细胞之间的细胞间隙进行移行。我们的结果提示，Cx43的异常表达在腹膜转移中起重要作用，Cx43介导的胃癌细胞与间皮细胞间的异源GJIC可能是转移过程中的重要调控步骤。最后，我们观察到，脱落的胃癌细胞通过间皮屏障分离是一条可行的细胞旁迁移途径。
The process of peritoneal metastasis involves the diapedesis of intra-abdominal exfoliated gastric cancer cells through the mesothelial cell monolayers; however, the related molecular mechanisms for this process are still unclear. Heterocellular gap-junctional intercellular communication (GJIC) between gastric cancer cells and mesothelial cells may play an active role during diapedesis. In this study we detected the expression of connexin 43 (Cx43) in primary gastric cancer tissues, intra-abdominal exfoliated cancer cells, and matched metastatic peritoneal tissues. We found that the expression of Cx43 in primary gastric cancer tissues was significantly decreased; the intra-abdominal exfoliated cancer cells and matched metastatic peritoneal tissues exhibited increasing expression compared with primary gastric cancer tissues. BGC-823 and SGC-7901 human gastric cancer cells were engineered to express Cx43 or Cx43T154A (a mutant protein that only couples gap junctions but provides no intercellular communication) and were co-cultured with human peritoneal mesothelial cells (HPMCs). Heterocellular GJIC and diapedesis through HPMC monolayers on matrigel-coated coverslips were investigated. We found that BGC-823 and SGC-7901 gastric cancer cells expressing Cx43 formed functional heterocellular gap junctions with HPMC monolayers within one hour. A significant increase in diapedesis was observed in engineered Cx43-expressing cells compared with Cx43T154A and control group cells, which suggested that the observed upregulation of diapedesis in Cx43-expressing cells required heterocellular GJIC. Further study revealed that the gastric cancer cells transmigrated through the intercellular space between the mesothelial cells via a paracellular route. Our results suggest that the abnormal expression of Cx43 plays an essential role in peritoneal metastasis and that Cx43-mediated heterocellular GJIC between gastric cancer cells and mesothelial cells may be an important regulatory step during metastasis. Finally, we observed that the diapedesis of exfoliated gastric cancer cells through mesothelial barriers is a viable route of paracellular migration.
登录
查看更多内容
连接蛋白43介导的间隙连接通信增强了培养中的乳腺肿瘤细胞尿。
DOI：
10.1186/bcr1042
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Pollmann MA;Shao Q;Laird DW;Sandig M
通讯作者：
Sandig M
影响因子：
9.3
作者：
Elzarrad MK;Haroon A;Willecke K;Dobrowolski R;Gillespie MN;Al-Mehdi AB
通讯作者：
Al-Mehdi AB
影响因子：
11.2
作者：
McLachlan, Elizabeth;Shao, Qing;Laird, Dale W.
通讯作者：
Laird, Dale W.
影响因子：
11.2
作者：
Langlois, Stephanie;Cowan, Kyle N.;Laird, Dale W.
通讯作者：
Laird, Dale W.
影响因子：
2.5
作者：
Takahashi-Iwanaga, Hiromi;Nio-Kobayashi, Junko;Furuya, Kishio
通讯作者：
Furuya, Kishio