We previously described an inverse correlation between galectin-9 (Gal-9) expression and
metastasis in patients with
malignant melanoma and
breast cancer. This study verified the ability of Gal-9 to inhibit lung
metastasis in experimental mouse models using highly metastatic B16F10
melanoma and Colon26
colon cancer cells. B16F10 cells transfected with a secreted form of Gal-9 lost their metastatic potential. Intravenous Gal-9 administration reduced the number of
metastases of both B16F10 and Colon26 cells in the lung, indicating that secreted Gal-9 suppresses
metastasis. Analysis of adhesive molecule expression revealed that B16F10 cells highly express CD44,
integrin alpha1, alpha 4, alpha V, and beta1, and that Colon26 cells express CD44,
integrin alpha2, alpha 5, alpha V, and beta1, suggesting that Gal-9 may inhibit the adhesion of
tumor cells to vascular endothelium and the extracellular matrix (ECM) by binding to such adhesive molecules. Indeed, Gal-9 suppressed the binding of
hyaluronic acid to CD44 on both B16F10 and Colon26 cells, and also suppressed the binding of
vascular cell adhesion molecule-1 to
very late antigen-4 on B16F10 cells. Furthermore, Gal-9 inhibited the binding of
tumor cells to ECM components, resulting in the suppression of
tumor cell migration. The present results suggest that Gal-9 suppresses both attachment and invasion of
tumor cells by inhibiting the binding of adhesive molecules on
tumor cells to
ligands on vascular endothelium and ECM.