A Novel Ex Vivo Peritoneal Model to Investigate Mechanisms of Peritoneal Metastasis in Gastric Adenocarcinoma

Peritoneal metastases (PM) portend limited survival in patients with Gastric Adenocarcinoma (GCa), and strategies to prevent and/or more effectively treat PM are needed. Existing models are limited in recapitulating key elements of the peritoneal metastatic cascade. To explore the underlying cellula...

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Bibliographic Details
Published inbioRxiv
Main Authors Ng, Deanna, Ali, Aiman, Lee, Kiera, Eymael, Denise, Abe, Kento, Luu, Shelly, Kazazian, Karineh, Brar, Savtaj, Conner, James, Magalhaes, Marco, Swallow, Carol J
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.11.2021
Subjects
Adenocarcinoma
Cancer
E-cadherin
Fluorescence microscopy
Genetic factors
Mesenchyme
Metastases
Molecular modelling
Patients
Peritoneum
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Summary:Peritoneal metastases (PM) portend limited survival in patients with Gastric Adenocarcinoma (GCa), and strategies to prevent and/or more effectively treat PM are needed. Existing models are limited in recapitulating key elements of the peritoneal metastatic cascade. To explore the underlying cellular and molecular mechanisms of PM, we have developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were obtained from patients undergoing abdominal surgery and suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent stained AGS human GCa cells for 24hrs, then washed and cultured for a further 3 days. Implantation and invasion of GCa cells within the explant were examined using real-time confocal fluorescence microscopy. Superficial implantation of AGS GCa cells within the mesothelial surface was readily detected, and colonies expanded over 3 days. To investigate the sensitivity of the model to altered GCa cellular implantation, we stably transfected AGS cells with E-Cadherin, restoring the E-Cadherin that they otherwise lack. This markedly suppressed implantation and invasion of AGS cells into the submesothelial mesenchymal layer. Here we show that this ex vivo human peritoneal explant model is responsive to manipulation of genetic factors that regulate peritoneal implantation and invasion by GCa cells, with reproducible results. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.11.15.468687