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

• Published in: Clinical cancer research 2005-04, Vol.11 (8), p.2962-2968
• Main Authors: IRIE, Akemi, YAMAUCHI, Akira, HIRASHIMA, Mitsuomi, KONTANI, Keiichi, KIHARA, Minoru, LIU, Dage, SHIRATO, Yukako, SEKI, Masako, NISHI, Nozomu, NAKAMURA, Takanori, YOKOMISE, Hiroyasu
• Format: Article
• Language: English
• Subjects: Adult; aggregation; Animals; Antineoplastic agents; Biological and medical sciences; Blotting, Western; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Adhesion; Cell Aggregation; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Extracellular Matrix Proteins - metabolism; Female; Follow-Up Studies; Galectins - analysis; Galectins - genetics; Humans; Immunohistochemistry; invasion; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Medical sciences; metastasis; Mice; Mice, Nude; Middle Aged; Neoplasm Metastasis; Neoplasm Transplantation; Pharmacology. Drug treatments; Plasmids - genetics; Prognosis; Transfection; Transplantation, Heterologous
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0861

Purpose: Galectin-9, a member of the β-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.