The KAI1 gene is identified as a
tumor metastasis suppressor gene in many types of
cancer. We examined KAI1 gene and its
protein KAI1/CD82 expression by in situ hybridization and immunohistochemical analysis, and found that KAI1
mRNA and
protein expression were inversely correlated with lymph node and distant
metastasis in digestive tract
carcinomas, but not with age and gender of the patient, or with
tumor differentiation. Moreover, KAI1/CD82
protein expression positively reflected the survival outcome of patients. Western blot analysis showed that
VP-16 increased KAI1/CD82
protein expression obviously in various
cancer cell lines, especially in those that were highly metastatic. This increased KAI1/CD82 expression was associated with its translocation from the cytomembrane to the nucleus, in which it interacted with nuclear p53
protein, forming a strong complex, observed by confocal microscopy and co-immunoprecipitation, respectively. In nude mice, after feeding with
VP-16, the number of
tumors metastasized from spleen to liver was obviously reduced, and KAI1/CD82
protein expression became stronger in those metastatic
tumors. Accordingly, this demonstrated that KAI1 might be used as an
indicator for predicting the clinical outcome, and
VP-16 may be clinically considered as a promising candidate for anti-
metastasis with regard to its potential to upregulate KAI1 expression.