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

作者：Bo Tang, Zhihong Peng, Pei-wu Yu, Ge Yu, Feng Qian, Dong-zhu Zeng, Yongliang Zhao, Yan Shi, Yingxue Hao, Hua-xing Luo · 发表于：PLoS ONE · 年份：2013 · DOI：10.1371/journal.pone.0074527 · 被引用次数：53 · 研究领域：Connexins and lens biology、Heat shock proteins research

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 ...