- The Caco-2 cell line, derived from human colorectal adenocarcinoma, has been widely used in gastrointestinal research and has made valuable contributions to the study of Helicobacter pylori–host interactions. Although not of gastric origin, Caco-2 cells are particularly relevant due to their ability to differentiate spontaneously into enterocyte-like cells when cultured over time. Upon differentiation, they develop key features of polarized intestinal epithelial cells, including apical-basolateral polarity, tight junctions, adherens junctions, brush border microvilli, and functional barrier properties—making them suitable for modeling the epithelial barrier function in vitro.
- In H. pylori research, Caco-2 cells have been used to investigate bacterial adhesion, barrier disruption, and translocation of bacterial products. Their well-developed tight junctions allow for quantitative measurements of epithelial integrity, such as transepithelial electrical resistance (TEER) and paracellular permeability assays using tracers like FITC-dextran or albumin. These assays have shown that H. pylori, particularly strains expressing CagA, can compromise barrier function in Caco-2 monolayers, leading to increased permeability and weakening of cell–cell adhesion.
- Caco-2 cells have also been employed to study CagA translocation and its downstream effects, including cytoskeletal rearrangement, loss of junctional proteins like ZO-1 and E-cadherin, and activation of β-catenin signaling pathways. While the efficiency of CagA delivery into Caco-2 cells may be lower compared to gastric-derived lines like AGS or NCI-N87, these cells are still useful for confirming effects on junctional integrity and epithelial permeability in a more physiologically organized epithelial context.
- Moreover, Caco-2 cells have been used in co-culture models with immune cells or in Transwell systems to simulate luminal exposure and immune surveillance, helping to dissect how H. pylori components may modulate the mucosal barrier and immune responses indirectly, even beyond the stomach.
- In summary, although not derived from gastric tissue, the Caco-2 cell line provides a differentiated, polarized epithelial model that has contributed significantly to understanding barrier dysfunction and epithelial responses during H. pylori infection. Its use complements gastric models by offering insights into general epithelial responses and barrier-related pathogenesis mechanisms.
