3965

LGALS9

lectin, galactoside-binding, soluble, 9;LGALS9;lectin, galactoside-binding, soluble, 9

ecalectin|gal-9|galectin 9|galectin-9|tumor antigen HOM-HD-21|urate transporter/channel protein

17q11.2

protein-coding

PURPOSE: Galectin-9, a member of the beta-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.

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

Oral squamous cell carcinomas (OSCCs), a major public health problem worldwide, are the most common neoplasms of the head and neck. The most important prognostic indicator for patients with OSCC is metastasis to cervical lymph nodes or distant organs. Galectin-9 is correlated with cellular adhesion and aggregation in melanoma cells. To investigate expression levels of galectin-9 mRNA and protein, we performed qRT-PCR and Western blot analyses on OSCC cell lines (Ca9-22, HSC-2, and HSC-3) and normal oral keratinocytes (NOKs). Galectin-9 mRNA and protein were commonly down-regulated in OSCC cell lines compared with NOKs. We further analyzed Ca9-22, which had the lowest expression of galectin-9. We then transfected the galectin-9 cDNA into Ca9-22 cells to examine whether overexpression of galectin-9 increases cellular adhesion in vitro. An adhesion assay using a fibronectin and collagen I coating plate revealed an increased cellular adherence ratio in overexpressed galectin-9 cells compared with nontransfected cells (p < 0.05). The data suggest that galectin-9 is correlated with oral cancer cell-matrix interactions and may therefore play an important role in the metastasis of OSCCs.