Developmental regulation, expression, and apoptotic potential of galectin-9, a beta-galactoside binding lectin.

Abstract

Galectin-9, a ␤ -galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, and adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed and its expression was developmentally regulated. In situ hybridization studies revealed an accentuated expression of galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. The high expression of galectin-9 in the thymus led us to investigate its role in the clonal deletion of thymocytes. Fusion proteins were generated, which retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at 2.5 M concentration, induced apoptosis in ‫ف‬ 30% of the thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end labeling method. The apoptotic effect was dose dependent and lactose inhibitable. At higher concentrations, it induced homotypic aggregation of the thymocytes. Electron microscopy revealed ‫ف‬ 60% of the thymocytes undergoing apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9. Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these findings indicate that galectin-9, a developmentally regulated lectin, plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus. ( J. Clin. Invest. 1997. 99:2452-2461.)

Galectin-9 Acts as a Prognostic Factor with Antimetastatic Potential in Hepatocellular Carcinoma

“…In addition to the anti-metastatic roles of Gal-9 mentioned above, it had been reported that Gal-9 induced apoptosis in T cells (Wada et al, 1997;Tsuchiyama et al, 2000), malignant melanoma cells (Kageshita et al, 2002) and breast cancer cells (Irie et al, 2005), and the pro-apoptotic role was required for galectin-9-induced suppression of melanoma and breast cancers (Kageshita et al, 2002;Irie et al, 2005). Kobayashi et al (2010) confirmed that Gal-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways.…”

“…The process of metastasis involves five critical steps: detachment of cancer cells from primary sites, movement (invasion) of cancer cells in ECM, attachment of cancer cells to vascular endothelial cells at distal sites, invasion of cancer cells through vascular endothelium, and tumor growth with neovascularization, which are essential for accomplishing malignant tumor metastasis (Wada et al, 1997). According to the present study we can find that Gal-9 suppressed multiple steps of metastasis by promoting cell aggregation, inhibiting adhesion and invasion of cancer cells to ECM, blocking cell-endothelial adhesion and obstructing trans-endothelium invasion of the tumor cells, which supported the hypothesis that Gal-9 prevent metastasis of hepatocarcinoma cells.…”

Retracted: A modified version of galectin‐9 suppresses cell growth and induces apoptosis of human T‐cell leukemia virus type I‐infected T‐cell lines

“…Although galectin-1 and -3 have been well studied among the various galectins, we do not have enough information on galectin-9. Wada et al 12 showed that galectin-9 induces mouse thymocyte apoptosis. We have found that HTLV-Iinfected T-cell lines and ATL cells from different patients are more susceptible to growth inhibition induced by treatment with hG9NC(null) than normal PBMCs.…”

“…10 Recent studies suggested that galectin-9 is a modulator of immune functions; it induces chemotaxis of eosinophils 11 and apoptosis of thymocytes, suggesting a possible role in the process of negative selection occurring during T-cell development. 12 With the objective of finding newer agents for the treatment of ATL, the present study was designed to investigate the antitumor potential of galectin-9 on HTLV-I-infected T-cell lines and primary ATL cells in vitro and in vivo, and the possible mechanisms involved in such antitumor activities. Since the protease susceptibility of galectin-9 makes it difficult to efficiently carry out in vivo experiments with recombinant proteins, we used the protease-resistant galectin-9 by modification of its linker peptide, hG9NC(null), in this study.…”

Determination of specific interactions between glucose ligand carrying polymer and glucose transporter type‐1 (GLUT‐1) using different cell types

“…[1][2][3][4] Significant progress has been made in the use of synthetic glycopolymers that mimic the role of carbohydrates in biological systems, to promote cell recognition characteristics. 5 Therefore, biomimetic glycopolymers have been designed to activate cell surfaces and control cell adhesion.…”