Toll-like receptors TLR4, TLR5 and TLR9 on gastric carcinoma cells: an implication for interaction with Helicobacter pylori.
In the human stomach Toll-like receptors (TLRs) expressed by the gastric epithelium interact with Helicobacter pylori and mediate production of proinflammatory cytokines and chemokines during H. pylori infection. This results in chronic active gastritis, the background from which gastric carcinoma arises via the epithelial precursor lesions, intestinal metaplasia and dysplasia. Therefore, the question is arising whether gastric carcinoma cells are also able to interact with H. pylori. In this study, TLR4, TLR5 and TLR9 expression was investigated on tumor cells of gastric carcinoma and on its precursor lesions, intestinal metaplasia and dysplasia, by immunohistochemistry. Gastric epithelium with intestinal metaplasia (n=10) and dysplasia (n=3) expressed TLR4 and TLR5. TLR4 was strongly expressed by tumor cells of 17 out of 22 and TLR5 by tumor cells of all 22 patients with gastric carcinoma. TLR9, however, was not detectable in intestinal metaplasia or dysplasia and only focally in 6 out of 22 gastric carcinomas. In contrast to H. pylori gastritis, epithelial TLR expression in intestinal metaplasia, dysplasia and gastric carcinoma was diffusely distributed without subcellular polarization as demonstrated by confocal microscopy. This is the first study describing TLR expression on tumor cells of gastric carcinoma and its precursor lesions. Expression of TLRs enables gastric carcinoma cells to interact with H. pylori. As H. pylori can induce gastric carcinoma-promoting factors, such as IL-8, via epithelial TLR expression, TLR expression by gastric carcinoma cells may have a dangerous potential.
Schmausser
Bernd
B
Institut für Pathologie, Universität Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. schmausser@web.de
Andrulis
Mindaugas
M
Endrich
Simon
S
Müller-Hermelink
Hans-Konrad
HK
Eck
Matthias
M
D004847:Epithelial Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005753:Gastric Mucosa / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D005756:Gastritis / Q000276:immunology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007120:Immunochemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000378:metabolism; D008679:Metaplasia; D018613:Microscopy, Confocal; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; C495346:TLR5 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors