[Expression of variant CD44 in colorectal cancer and its relationship to liver metastasis]

A number of different isoforms of CD44 generated by alternative splicing have been isolated and sequenced. There have been several reports that CD44v plays a role in the steps of the metastatic process. We examined the role of the variant CD44v8-10 in metastases of human colon cancer cell line HT29m using a monoclonal antibody reactive with the v9 product (mAb 44-1V). Pretreatment with mAb 44-1V prevented the formation of liver metastases. In addition, we found that the attachment of HT29m cells to the basement membrane matrix was inhibited by mAb 44-1V. Several reports have shown correlations between metastatic potential and expression of CD44v in human colorectal cancer. We demonstrated that CD44v8-10 and CD44v6 RNA expression was higher in carcinomas associated with liver metastases than in those without by Northern blotting. We analyzed the expression of the CD44v8-10 product in colorectal cancer immunohistochemically using mAb 44-1V, and evaluated its prognostic significance. There were significant correlations between CD 44v8-10 immunoreactivity and both lymph node and liver metastases. Patients with CD44v8-10-positive tumors had a greater relative risk of death compared with those whose tumors were CD44v8-10 negative. These results suggest that CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance.