INCREASED EXPRESSION OF S100A4, A METASTASIS-ASSOCIATED GENE, IN HUMAN COLORECTAL ADENOCARCINOMAS

The S100A4 gene (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin/FS P1/CAPL) encoding an S100-related calcium-binding protein is implied t o be involved in the invasion and metastasis of murine tumor cells. In the present study, the expression of S100A4 in human colorectal adeno carcinoma cell lines (SW837, LoVo, DLD-1, HT-29, SW480, SW620, WiDr, a nd Colo201) and surgically resected neoplastic tissues was examined to investigate whether S100A4 plays a role in the invasion and metastasi s of human tumor cells. Northern blot analysis using total RNA isolate d from the adenocarcinoma cell lines revealed that five of the eight c ell lines expressed substantial amounts of S100A4 mRNA. Normal colon f ibroblasts (CCD-18Co) expressed little of the RNA. Using surgically re sected specimens, it seemed that the amount of S100A4 mRNA in adenomas was nearly equal to that in normal colonic mucosa, whereas adenocarci nomas expressed a significantly higher amount of the RNA than did the adjacent normal colonic mucosa. Immunohistochemical analysis using for malin-fixed paraffin-embedded surgical specimens and monoclonal anti-S 100A4 antibody demonstrated that none of 12 adenoma specimens were imm unopositive, whereas 8 of 18 (44%) focal carcinomas in carcinoma in ad enoma specimens and 50 of 53 (94%) adenocarcinoma specimens were immun opositive. Interestingly, the incidence of immunopositive cells increa sed according to the depth of invasion, and nearly all of the carcinom a cells in 14 metastases in the liver were positive. These results sug gest that S100A4 may be involved in the progression and the metastatic process of human colorectal neoplastic cells.