Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene.

KAI1 is a potential metastatic suppressor gene for prostate cancer. We found by Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines exhibited undetectable or very low expression level of KAI1 mRNA. The effects of KAI1 on the adhesion, motility and invasiveness of colon cancer cells was therefore investigated by using two kinds of stable transfectants, i.e., antisense transfectants of BM314 cells whose KAI1 mRNA expression was suppressed by transfer of antisense KAI1 cDNA and sense transfectants of DLD-1 cells with the enhanced KAI1 mRNA by sense cDNA transfer. The following results were obtained: (1) KAI1 gene expression had no significant effect on in vitro cell growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay showed that KAI1 enhanced the Ca++-independent aggregatability of those colon cancer cells; (3) It was revealed by cell motility and invasion assays that KAI1 suppressed both the motility and in vitro invasiveness of those cells and (4) Furthermore, both the binding to fibronectin and the migration on fibronectin-coated plates of those cells were inhibited by KAI1 expression. These suggest that reduced KAI1 gene expression may contribute to the invasiveness and metastatic ability of colon cancer cells.