| KAI1, a new identified metastatic suppressor gene, is located on human chromosome lip 11.2. It was originally isolated by Dong in 1995. KAI1 mRNA is ubiquitously expressed with abundant expression in the surface epithelium of the major epithelial tissues, including prostate, breast, bladder, and Pancreas. Its protein product, CD82, belongs to TM4SF (transmembrane four superfamily) or TST (tetra span transmembrane) superfamily, many of which, including KAI1, are CD antigens present on the surface of leukocytes. Four hydrophobic transmembrane domains and one large extracellular hydrophilic domain containing 3 potential N-glycosylation sites are thought to function in cell-cell and cell-matrix interactions. KAI1 and other TM4SF members have been demonstrated to bind to each other, integrins, E-cadherin, and other surface molecules to relay extracellular signals to signal transduction pathways that are important in cellular adhesion, invasion motility, and metastasis suppression.To study the correlation of KAI1 with colorectal carcinoma, the expression of KAI1 was detected by in situ hybridization and immumohistochemistry in paraffin-embedded normal colonic epithelium, carcinoma and lymphatic metastasis. The results indicated that KAI1/CD82 is significantly higher expressed in colorectal carcinoma compared with normal colonic epithelium and lymphatic metastasis (P<0.05) . The expression of KAI1/CD82 had no relationship with histological grade (P>0.05 ) . The expression in Dukes A,B carcinoma is higher in comparison with Dukes C carcinoma (P<0.05) whatever in mRNA or protein level and the expression of Dukes C carcinoma is down-regulated. The expression in metastasis is almost loss. These data demonstrate KAI1expression increase in an earlier tumor stage of colorectal carcinoma, decrease in advanced stages, and are possibly lost in metastases. This indicated that the expression of KAI1 had reverse correlation with metastasis in colorectal carcinoma. KAI1/CD82 may be a useful indicator of prognosis in colorectal carcinoma.To further study the effect of KAI1 expression on colorectal carcinoma cell, KAI1 cDNA was transfected into highly malignant colorectal carcinoma cell line, LoVo, which has low levels of endogenous KAI1 expression. The expressions of KAI1 mRNA and protein were determined by immunohistochemistry and in situ hybridization. The biological behaviors of the KAI1-transfected LoVo cells were investigated by cell-cell adhesion, cell aggregation, cell-matrix adhesion and invasion assays. Our results show that KAI1 expression significantly suppressed the metastatic potential of KAI1-transfected LoVo cells. Metastasis suppression correlated with the increased adhesion to homotypic cells and reduced tumor adhesion to extracellular matrix components. The KAI1 transfectant cells exhibited significantly increased homotypic cell aggregation in comparison with the control transfectant cells. This aggregation of the KAI1 transfectants was further enhanced upon exposure to anti-CD82 antibody. Furthermore, compared with the control, KAI1 expression significantly suppressed the in vitro cell invasion in KAI1-transfected LoVo cells (P<0.05).In word, our results suggested that KAI1 might function as a negative regulator of colorectal carcinoma metastasis and have a significant meaning in prognosis and treatment.
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