French National Cancer Institute (INCa).

Background and aims-The Tage4 gene (tumour associated glycoprotein E4) is overexpressed in rat colon tumours and Min mouse intestinal adenomas. The rat Tage4 protein has approximately 40% identity with human CD155, a member of the immunoglobulin superfamily coding for a transmembrane protein capable of serving as an entry receptor for poliovirus, porcine pseudorabies virus, and bovine herpesvirus 1. Analysis of the rat Tage4 gene has revealed structural and functional similarities with the human CD155 gene. We therefore investigated expression of the CD155 gene in human colorectal carcinomas. Methods-Overall CD155 expression was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis using tissue specimens from patients with colorectal adenomas and adenocarcinomas. We also used a qualitative RT-PCR assay to determine relative expression of diVerent splicing variants in each sample. Results-mRNA levels of CD155 were increased in six of six colorectal cancer tissues compared with the tumour free colon mucosa. Immunohistochemical analysis revealed an increased level of CD155 protein in 12 of 12 samples. The qualitative RT-PCR assay revealed that relative expression of the diVerent CD155 variant transcripts was similar in the diVerent normal and cancer samples tested, indicating that this overexpression is not associated with a particular mRNA variant generated by alternative splicing of the CD155 gene. Conclusion-We have shown for the first time that the CD155 gene is overexpressed in colorectal carcinoma and that this overexpression begins at an early stage in tumorigenesis and continues to late stages. (Gut 2001;49:236-240) Keywords: CD155; colorectal cancer; immunoglobulin superfamily; poliovirus receptor As our understanding of the biology of colorectal cancer progresses, new knowledge about tumorigenesis and tumour biology can be used to diagnose, treat, and prevent this type of cancer. In an initial study of an animal model for immunotherapy of colon tumours, monoclonal antibodies directed against rat colon carcinoma cells were raised.

Although the enteric nervous system (ENS) has been shown to regulate various mucosal functions, its role in the physiological control of the human intestinal epithelial barrier is unknown. The aim of this study was to investigate whether the ENS is able to modulate epithelial barrier permeability and a key tight junction-associated protein, zonula occludens-1 (ZO-1). Therefore, we developed a co-culture model, consisting of human submucosa containing the submucosal neuronal network and human polarized colonic epithelial monolayers (HT29-Cl.16E or Caco-2). Submucosal neurons were activated by electrical field stimulation (EFS). Permeability was assessed by measuring the flux of paracellular permeability markers (FITC-dextran or FITC-inulin) across epithelial monolayers. Expression of ZO-1 was determined by immunofluorescence, quantitative immunoblot analysis, and real time RT-PCR. Using the coculture model, we showed that EFS of submucosal neurons resulted in a reduction in FITC-dextran or FITC-inulin fluxes, which was blocked by TTX. In HT29-Cl.16E, the effect of submucosal neuron activation was blocked by a VIP receptor antagonist (VIPra) and reproduced by VIP. Furthermore, ZO-1 expression (mRNA, protein) assessed in HT29-Cl.16E, was significantly increased after submucosal neuron activation by EFS. These effects on ZO-1 expression were blocked by TTX and VIPra and reproduced by VIP. In conclusion, our results strongly suggest a modulatory role of VIPergic submucosal neuronal pathways on intestinal epithelial barrier permeability and ZO-1 expression.