Expression of adhesion molecules and mucins in human and rhesus macaque gastrointestinal epithelial cells.

Epithelial junctions and mucins play key roles in the gastrointestinal mucosal barrier, and their alterations are associated with numerous diseases, including carcinomas. The systematic expression of adhesion molecules and mucins in normal and malignant human gastrointestinal cells was investigated in this study. In normal human gastrointestinal cells, zonula occludens-1 (ZO-1), α-catenin, ß-catenin, γ-catenin and desmoglein-2 (DSG2) were located in the cytoplasmic membranes, whereas symplekin stained in the nuclei. ZO-1, the three catenins, and DSG2 were observed in the gastric and colorectal carcinomas with reduced and heterogeneous expression and with abnormal distribution. Symplekin was detected in the nuclei of tumor cells in most tumors but not observed in some others. The immunohistochemical results for ZO-1 and symplekin on the tissues were consistent with the data for the cultured cells obtained by immunocytochemical staining and Western blot analysis. MUC1 was not stained in the normal gastrointestinal cells without periodate oxidation, but it was strongly labeled in the malignant gastrointestinal cells. MUC2 was detected in the normal and malignant gastrointestinal cells without the periodate treatment. These findings indicate that alterations in the expression of the epithelial junctions and mucins are associated with the malignant transformation of gastrointestinal cells. In addition, the gastrointestinal epithelial cells of rhesus macaques expressed these adhesion molecules and mucins, as did the human cells, suggesting that the rhesus monkey is a suitable experimental animal model for research on adhesion molecules and mucins.

Alteration of adhesion molecule expression and cellular polarity in hepatocellular carcinoma.

AIMS: To study the expression of adhesion molecules in human liver and their possible roles during hepatocarcinogenesis. METHODS AND RESULTS: The expression of adhesion molecules in normal liver tissues, benign including probable premalignant lesions and malignant lesions was systematically investigated by immunohistochemistry and Western blotting. In normal liver, both hepatocytes and bile duct cells expressed symplekin, desmoglein 1/2, desmocollin 2, desmoplakin and plakophilin 2, but did not express desmocollin 1/3 or plakophilin 1. In benign hepatocyte lesions, expression of the adherens junctions and desmosomes was uniform and slightly increased, but symplekin appeared to show reduced expression in dysplastic lesions. In hepatocellular carcinoma (HCC), the expression of adhesion molecules was often heterogeneous and of abnormal location. Tumour cells with an abnormal distribution or loss of adhesion molecules showed an apolar arrangement of tissue architecture. The expression levels of the adhesion molecules correlated with the differentiation grades of HCC cells. CONCLUSIONS: The decreased expression of symplekin may be an early step in the transformation of hepatocytes, whereas alteration of the expression of adherens junctions and desmosomes may indicate more serious changes.