The chemokine receptor CCR7 is expressed on epithelium of non-inflamed gastric mucosa, Helicobacter pylori gastritis, gastric carcinoma and its precursor lesions and up-regulated by H. pylori.
CCR7 chemokine-receptor expression on tumour cells of gastric carcinoma has been associated with lymph-node metastasis and is thought to play an important role in metastasis. However, so far it is unknown whether CCR7 is newly up-regulated on gastric carcinoma or already expressed in non-neoplastic gastric epithelium. Therefore, epithelial CCR7 expression was investigated in the process of gastric carcinogenesis: non-inflamed mucosa --Helicobacter pylori gastritis -- intestinal metaplasia/dysplasia -- gastric carcinoma. CCR7 was expressed by gastric epithelium in non-inflamed gastric mucosa (n = 5), H. pylori gastritis (n = 17), intestinal metaplasia (n = 10), dysplasia (n = 3) and on tumour cells in 20 of 24 patients with gastric carcinoma (13/14 intestinal-type; 7/10 diffuse-type) as tested by immunohistochemistry. As CCR7 expression by gastric epithelium was significantly stronger in H. pylori gastritis than in non-infected mucosa, the influence of H. pylori on CCR7 receptor expression of gastric epithelial cells was investigated by fluorescence activated cell sorter analysis. H. pylori strains up-regulated the CCR7 chemokine-receptor in CCR7-positive cell lines. No difference in CCR7 up-regulation between cag(+) and cag(-)H. pylori strains was found. Epithelial CCR7 up-regulation by H. pylori may alter the metastatic fate of gastric carcinoma. Additionally, CCR7 expression not only on gastric carcinoma, but also on non-neoplastic gastric epithelium, suggests a novel biological function.
Schmausser
B
B
Institut für Pathologie, Universität Würzburg, Würzburg, Germany. schmausser@web.de
Endrich
S
S
Brändlein
S
S
Schär
J
J
Beier
D
D
Müller-Hermelink
H-K
HK
Eck
M
M
D002277:Carcinoma / Q000276:immunology*; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology*; D005756:Gastritis / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D011230:Precancerous Conditions; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology*
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine