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Helicobacter pylori is the main cause of peptic ulceration and gastric mucosa-associated lymphoid tissue lymphoma, 1, 2 and the strongest risk factor for the development of distal gastric adenocarcinoma. 3 The outcome of H pylori infection is dependent on the host 4 and environmental 5 and bacterial factors. 6, 7 Strains possessing the Cag pathogenicity island, encoding a type IV bacterial protein secretion system, 8, 9, 10, 11 are more strongly associated with increased levels of inflammation and disease 6 as are those producing an active form of VacA, a pore-forming toxin that induces cytoplasmic vacuolation in vitro. 12- 15
The cadherin-catenin complex is the key component of the adherens junction between epithelial cells. It is important in providing structural support to cells by linkage with the actin cytoskeleton, and also in promoting epithelial cross-talk. Changes in expression of proteins in this complex are implicated in several epithelial cancers including gastric adenocarcinoma, 16- 21 and germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. 22, 23 β-catenin is also an important cell signalling molecule (part of the wnt pathway) and has an important role in cell proliferation and oncogenesis.
Few data are available at present on expression of the cadherins and catenins in normal and inflamed gastric epithelial cells. A few reports suggest that H pylori disrupts E-cadherin 24- 26 and stimulates β-catenin signalling, 27 and also that these mechanisms underlie gastric carcinogenesis. We assessed whether H pylori disrupted E-cadherin and β-catenin localisation in relevant cell lines, whether this resulted in β-catenin-mediated cell signalling and whether H pylori infection was associated with changes in E-cadherin and β-catenin immunolocalisation in vivo.
METHODS
In vitro studies
H pylori strains and epithelial cells
The following strains were used:
60190 (ATCC 49503, cagPaI +, VacA s1m1 (vacuolating) 13 )
Tx30a (ATCC 51392, cagPaI -, VacA s2m2 (non-vacuolating) 13 )
60190CagE- (cagE - insertion isogenic mutant of 60190 28 )
60190VacA- (disrupted VacA - insertion mutant of 60190 29 )
AGS, RK13, HeLa and HT29 cell lines were used for coculture 28 and grown in Lab-Tek chamber slides (Nunc, Roskilde, Denmark) and 75-cm2 tissue culture flasks. After 48 h of incubation, H pylori was added to subconfluent HT29 cells such that the final ratio of...