Investigating the mechanisms of peritoneal metastasis in gastric adenocarcinoma using a novel ex vivo peritoneal explant model

Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells a...

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Bibliographic Details
Published in:Scientific reports 2022-07, Vol.12 (1), p.11499-11499, Article 11499
Main Authors: Ng, Deanna, Ali, Aiman, Lee, Kiera, Eymael, Denise, Abe, Kento, Luu, Shelly, Kazazian, Karineh, Lu, Yi Qing, Brar, Savtaj, Conner, James, Magalhaes, Marco, Swallow, Carol J.
Format: Article
Language:English
Subjects:
631/1647/767
631/67/1504
631/67/322
631/67/70
Adenocarcinoma
Cancer
Colorectal carcinoma
E-cadherin
Fluorescence microscopy
Fluorescent indicators
Gastric cancer
Humanities and Social Sciences
Metastases
Metastasis
Molecular modelling
multidisciplinary
Ovarian cancer
Peritoneum
Science
Science (multidisciplinary)
Transfection
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Summary:Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells and the peritoneal layer. To explore the underlying cellular and molecular mechanisms of peritoneal metastasis, we developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent dye stained AGS human gastric adenocarcinoma cells for 24 h, then washed thoroughly. Implantation of AGS cells within the explanted peritoneum and invasion beyond the mesothelial layer were examined serially using real-time confocal fluorescence microscopy. Histoarchitecture of the explanted peritoneum was preserved over 5 days ex vivo. Both implantation and invasion were suppressed by restoration of functional E-cadherin through stable transfection of AGS cells, demonstrating sensitivity of the model to molecular manipulation. Thus, our ex vivo human peritoneal explant model permits meaningful investigation of the pathways and mechanism that contribute to peritoneal metastasis. The model will facilitate screening of new therapies that target peritoneal dissemination of gastric, ovarian and colorectal cancer.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-13948-x