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Galectin-9 as a Prognostic Factor with Antimetastatic Potential in Breast Cancer

Authors' Affiliations: ¹ Second Department of Surgery and Departments of ² Cell Regulation, ³ Endocrinology and ⁴ Immunology and Immunopathology, School of Medicine, Kagawa University and ⁵ GalPharma Co. Ltd., Kagawa, Japan

Requests for reprints: Akira Yamauchi, Department of Cell Regulation, School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Phone: 81-87-891-2403; Fax: 81-87-891-2403; E-mail: yamauchi{at}kms.ac.jp.

Purpose: Galectin-9, a member of the ß-galactoside–binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer.

Experimental Design: Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years.

Results: MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9–positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9–positive patients was more favorable than that for the galectin-9–negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis.

Conclusions: Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.

Key Words: aggregation • invasion • metastasis

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