Inhibition of liver metastasis formation by anti-CD44 variant exon 9 monoclonal antibody

The overexpression of variants of the glycoprotein CD44 is thought to be associated with the tumorigenesis and progression of human cancers. We examined the role of the variant CD44v8-10 in the metastasis of the human colon cancer cell line HT29 using a monoclonal antibody (mAb 44-1V) reactive with the v9 product. After immunization with mAb 44-1V, the growth of HT29m cells in vitro was not retarded. Six-to 8-week-old mice were divided into 4 groups for liver metastasis assay. All animals in control groups injected with intrasplenic HT29m developed metastases. In contrast, only one of the animals injected with HT29m that reacted with mAb 44-1V developed a metastatic tumor in the liver. The intravenous administration of mAb 44-1V after intrasplenic HT29m injection did not inhibit the formation of liver metastasis. In addition, the adhesiveness of the HT29m cells to the basement membrane matrix was decreased by treatment with the anti-CD44v9 mAb. These findings indicated that a CD44 variant containing the products of variants of exons v8-10 may play an important role in adhesion of tumor cells to the capillaries of distant organs in the metastatic process.