title: Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices.
abstract: 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.
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Nobumoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Nagahara
authors.forename: Souichi
authors.initials: S
authors.lastname: Oomizu
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.forename: Nozomu
authors.initials: N
authors.lastname: Nishi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takeshita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Akira
authors.initials: A
authors.lastname: Tominaga
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D037161:Galectins / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use*; D006820:Hyaluronic Acid / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D037161:Galectins; C508186:galectin 9, mouse; D006820:Hyaluronic Acid