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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

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) betw...

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Autores principales: Tang, Bo, Peng, Zhi-hong, Yu, Pei-Wu, Yu, Ge, Qian, Feng, Zeng, Dong-zhu, Zhao, Yong-liang, Shi, Yan, Hao, Ying-xue, Luo, Hua-xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770585/
https://www.ncbi.nlm.nih.gov/pubmed/24040271
http://dx.doi.org/10.1371/journal.pone.0074527
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author Tang, Bo
Peng, Zhi-hong
Yu, Pei-Wu
Yu, Ge
Qian, Feng
Zeng, Dong-zhu
Zhao, Yong-liang
Shi, Yan
Hao, Ying-xue
Luo, Hua-xing
author_facet Tang, Bo
Peng, Zhi-hong
Yu, Pei-Wu
Yu, Ge
Qian, Feng
Zeng, Dong-zhu
Zhao, Yong-liang
Shi, Yan
Hao, Ying-xue
Luo, Hua-xing
author_sort Tang, Bo
collection PubMed
description 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.
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spelling pubmed-37705852013-09-13 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 Tang, Bo Peng, Zhi-hong Yu, Pei-Wu Yu, Ge Qian, Feng Zeng, Dong-zhu Zhao, Yong-liang Shi, Yan Hao, Ying-xue Luo, Hua-xing PLoS One Research Article 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. Public Library of Science 2013-09-11 /pmc/articles/PMC3770585/ /pubmed/24040271 http://dx.doi.org/10.1371/journal.pone.0074527 Text en © 2013 Tang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tang, Bo
Peng, Zhi-hong
Yu, Pei-Wu
Yu, Ge
Qian, Feng
Zeng, Dong-zhu
Zhao, Yong-liang
Shi, Yan
Hao, Ying-xue
Luo, Hua-xing
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770585/
https://www.ncbi.nlm.nih.gov/pubmed/24040271
http://dx.doi.org/10.1371/journal.pone.0074527
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