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Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression

Item Type:Article
Title:Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression
Creators Name:Anders, M. and Vieth, M. and Roecken, C. and Ebert, M. and Pross, M. and Gretschel, S. and Schlag, P.M. and Wiedenmann, B. and Kemmner, W. and Hoecker, M.
Abstract:Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R(0)-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P<0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.British Journal of Cancer advance online publication, 13 January 2009; doi:10.1038/sj.bjc.6604876 www.bjcancer.com.
Keywords:Coxsackie Adenovirus Receptor, Gastric Cancer, Prognosis, Migration, Invasion
Source:British Journal of Cancer
ISSN:0007-0920
Publisher:Nature Publishing Group (U.K.)
Volume:100
Number:2
Page Range:352-359
Date:27 January 2009
Official Publication:https://doi.org/10.1038/sj.bjc.6604876
PubMed:View item in PubMed

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