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

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.

• Authors: M Anders, M Vieth, C Röcken, M Ebert, M Pross, S Gretschel, P M Schlag, B Wiedenmann, W Kemmner, M Höcker
• Journal: British journal of cancer (Br J Cancer) Vol. 100 Issue 2 Pg. 352-9 (Jan 27 2009) ISSN: 1532-1827 [Electronic] England
• PMID: 19142187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLMP protein, human
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• RNA, Messenger
• Receptors, Virus

Topics

• Adenocarcinoma (metabolism, secondary)
• Adenoviridae (physiology)
• Adult
• Aged
• Aged, 80 and over
• Blotting, Western
• Cell Movement
• Cell Proliferation
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Enterovirus (physiology)
• Female
• Fluorescent Antibody Technique
• Gastric Mucosa
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Prognosis
• RNA, Messenger (genetics, metabolism)
• Receptors, Virus (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (metabolism, pathology)
• Tissue Array Analysis
• Transfection
• Tumor Cells, Cultured