- The AGS cell line, derived from a human gastric adenocarcinoma, has played a foundational role in advancing our understanding of Helicobacter pylori pathogenesis. As an epithelial cell line of gastric origin, AGS cells offer several advantages for in vitro studies, including ease of culture, high transfection efficiency, and consistent responsiveness to infection. Although they lack features such as full epithelial polarity and E-cadherin expression, AGS cells have become a gold standard model for dissecting the molecular mechanisms underlying H. pylori–host interactions.
- One of the most significant contributions of AGS cells has been in the study of the bacterial virulence factor CagA. AGS cells were instrumental in the initial discovery that CagA is translocated into host cells through the H. pylori Type IV secretion system (T4SS) and subsequently tyrosine-phosphorylated on specific EPIYA motifs. These phosphorylation events have downstream consequences on host cell signaling, and AGS cells have been widely used to explore these processes in detail. Studies in AGS cells have revealed that CagA can manipulate several key signaling pathways, including MAPK/ERK, PI3K/Akt, β-catenin, and NF-κB, contributing to changes in gene expression, inflammation, and cellular transformation.
- AGS cells are also known for their characteristic morphological response to CagA-positive H. pylori strains, known as the “hummingbird phenotype.” This phenotype, marked by cell elongation and scattering, reflects profound cytoskeletal rearrangements driven by CagA and has served as a visual marker of pathogenic activity in vitro. The ability of H. pylori to alter the morphology and behavior of AGS cells has provided key insights into the bacterium’s role in promoting oncogenic changes and disrupting epithelial homeostasis.
- Beyond CagA, AGS cells have been utilized to study the effects of other H. pylori factors, such as VacA, on apoptosis, DNA damage, and cell cycle regulation. These studies have shown that H. pylori can induce oxidative stress, chromosomal instability, and other genotoxic effects in AGS cells, supporting its classification as a Class I carcinogen by the World Health Organization.
- Despite their many advantages, AGS cells also have limitations. They are non-polarized and do not form tight junctions, which restricts their usefulness for studying barrier function and epithelial polarity. Additionally, the absence of E-cadherin limits their utility in investigating adherens junctions. For these reasons, researchers increasingly complement AGS-based experiments with polarized gastric cell lines (e.g., NCI-N87), non-gastric epithelial models (e.g., MDCK, Caco-2), and more physiologically relevant systems such as primary gastric cells and human gastric organoids.
- In summary, AGS cells have made enduring contributions to H. pylori research, particularly in elucidating CagA translocation, host cell signaling, and pathogenic outcomes. While newer models are helping to fill gaps in physiological relevance, AGS cells continue to be an indispensable tool for rapid, mechanistic studies of H. pylori–host cell interactions.
