Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices.
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.
Nobumoto
Atsuya
A
Department of Immunology and Immunopathology, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan.
Nagahara
Keiko
K
Oomizu
Souichi
S
Katoh
Shigeki
S
Nishi
Nozomu
N
Takeshita
Keisuke
K
Niki
Toshiro
T
Tominaga
Akira
A
Yamauchi
Akira
A
Hirashima
Mitsuomi
M
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
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D037161:Galectins; C508186:galectin 9, mouse; D006820:Hyaluronic Acid