Cell culture models for studying the development of Barrett's esophagus: a systematic review

P. Bus, P. D. Siersema, J. W. P. M. van Baal*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Background Barrett's esophagus (BE) is a premalignant condition caused by chronic gastroesophageal reflux. BE patients have an increased risk of developing esophageal adenocarcinoma (EAC). As many aspects of this condition are still unknown, there is a need for in vitro models to study BE development.

Aim To review the literature on cell lines and incubation conditions for studying BE development.

Methods A literature search was performed using PubMed, EMBASE and the Cochrane library, combining the words esophagus, cell line, culture, Barrett's, bile, acid, exposure, reflux and adenocarcinoma.

Results A wide range of cell lines and incubation conditions to study BE development have been reported. The most commonly used cell lines are derived from epithelium from patients with BE or EAC. A 25-minute incubation with 200 mu M bile salts induced cell proliferation and Akt phosphorylation. However, increased CDX2 and MUC2 expression was only observed with longer incubations or higher bile salt concentrations. Two-hundred mu M bile at pH 6 showed a higher toxicity to EAC cells than the same concentration at pH 7. Multiple 5-minute exposures with 200 mu M bile at pH 4 or pH 7 increased CK8/18 and COX2 in BE epithelial cells.

Conclusions Two-hundred mu M conjugated primary or secondary bile salts at pH 4 for multiple short exposures is able to induce BE specific factors in BE cell lines. In SQ and EAC cell lines; however, higher concentrations of secondary bile salts for 8 h are needed to induce BE specific molecules. Due to the high variability in reported methods, it is difficult to determine the most effective in vitro setup for studying the development of BE.

Original languageEnglish
Pages (from-to)149-161
Number of pages13
JournalCellular oncology
Volume35
Issue number3
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Bile salts
  • Acid
  • Reflux
  • Barrett's esophagus
  • In vitro model
  • Cell lines
  • NF-KAPPA-B
  • GASTROESOPHAGEAL-REFLUX DISEASE
  • MAPK-MEDIATED PROLIFERATION
  • NORMAL SQUAMOUS ESOPHAGUS
  • ACID DEOXYCHOLIC-ACID
  • BILE-ACIDS
  • DNA-DAMAGE
  • GENE-EXPRESSION
  • IN-VITRO
  • ADENOCARCINOMA CELLS

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