High yield reproducible rat model recapitulating human Barrett's carcinogenesis

Area of Science:

• Gastroenterology and Oncology
• Surgical Pathology
• Molecular Biology

Background:

• Human esophageal adenocarcinoma (EAC) is a significant health concern.
• Current models for studying EAC pathogenesis and progression have limitations.
• Efficient and reliable animal models are crucial for advancing EAC research.

Purpose of the Study:

• To establish and validate a modified Levrat model of end-to-side esophagojejunostomy in rats for EAC replication.
• To investigate the biological and pathological progression of EAC in this model.
• To analyze key gene expression changes during EAC development.

Main Methods:

• End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux.
• Animals were euthanized serially to collect esophageal tissues for histopathology and gene expression analysis.
• Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to assess the expression of MUC2, CK19, and CK20.

Main Results:

• The surgical model demonstrated a high EAC tumor burden (100% by 40 weeks) with observed metastasis.
• Histopathology revealed a progression from esophagitis to Barrett's esophagus (BE), then to dysplasia and EAC.
• Gene expression analysis showed downregulation of MUC2 and stepwise upregulation of CK19 and CK20 from BE to EAC.

Conclusions:

• The modified Levrat model provides an efficient method for replicating EAC in rats with low mortality.
• This model facilitates the study of EAC development, progression, and potential therapeutic strategies.
• The observed gene expression patterns correlate with EAC progression, offering molecular insights.