1. ¹Department of Internal Medicine, Division of Gastroenterology and Hepatology, Charité Medical School, Campus Virchow, Augustenburgerplatz 1, Berlin 13353, Germany
2. ²Institute of Pathology, Klinikum Bayreuth, Preuschwitzer Str. 101, Bayreuth 95445, Germany
3. ³Institute of Pathology, Charité Medical School, Charitéplatz 1, Berlin 10117, Germany
4. ⁴Department of Internal Medicine II, Technical University of Munich, Ismaninger Str. 22, Munich 81675, Germany
5. ⁵Department of Surgery, DRK Kliniken Berlin Köpenick, Salvador-Allende-Str. 2–8, Berlin 12559, Germany
6. ⁶Department of Surgery and Surgical Oncology, Robert Rössle Clinic Charité, Campus Buch, Lindenberger Weg 80, Berlin 13125, Germany
7. ⁷Max Delbrück Center of Molecular Medicine, Robert-Rössle-Strae 10, Berlin 13125, Germany
8. ⁸Center of Anatomy and Integrative Neuroanatomy, Charité Medical School, Campus Mitte, Charitéplatz 1, Berlin 10117, Germany

Correspondence: Dr M Anders, E-mail: mario.anders@charite.de

Revised 17 November 2008; Accepted 11 December 2008; Published online 13 January 2009.

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 R₀-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.