Fujihara Shintaro, Mori Hirohito, Kobara Hideki, Rafiq Kazi, Niki Toshiro, Hirashima Mitsuomi, Masaki Tsutomu
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
Recent Pat Endocr Metab Immune Drug Discov. 2013 May;7(2):130-7. doi: 10.2174/1872214811307020006.
Galectin-9 is a tandem-repeat type galectin with two carbohydrate-recognition domains, and it was first identified as an eosinophil chemoattractant and activation factor. Subsequent studies revealed that galectin-9, similar to other galectins, modulates a variety of biological functions including cell aggregation and adhesion, as well as apoptosis of tumor cells. Galectin-9 has recently been shown to have an anti-proliferative effect on cancer cells. Recent studies have uncovered additional mechanisms by which T cell immunoglobulin mucin-3 (Tim-3), a receptor for galectin-9, negatively regulates T cell responses by promoting CD8+ T cell exhaustion and inducing expansion of myeloid-derived suppressor cells. These mechanisms are involved in tumor growth and escape from immunity. In many solid cancers, the loss of galectin-9 expression is closely associated with metastatic progression, and treatment with recombinant galectin-9 prevents metastatic spread in various preclinical cancer models. Here, we review the biology and physiological role of galectin-9, and discuss the therapeutic potential of galectin-9 in cancer as well as relevant patents.
半乳糖凝集素-9是一种具有两个碳水化合物识别结构域的串联重复型半乳糖凝集素，最初被鉴定为嗜酸性粒细胞趋化因子和激活因子。随后的研究表明，与其他半乳糖凝集素类似，半乳糖凝集素-9可调节多种生物学功能，包括细胞聚集和黏附，以及肿瘤细胞的凋亡。最近发现半乳糖凝集素-9对癌细胞具有抗增殖作用。最近的研究揭示了半乳糖凝集素-9的受体T细胞免疫球蛋白黏蛋白-3（Tim-3）通过促进CD8+T细胞耗竭和诱导髓源性抑制细胞扩增来负向调节T细胞反应的其他机制。这些机制与肿瘤生长和免疫逃逸有关。在许多实体癌中，半乳糖凝集素-9表达的缺失与转移进展密切相关，在各种临床前癌症模型中，用重组半乳糖凝集素-9治疗可防止转移扩散。在此，我们综述了半乳糖凝集素-9的生物学和生理作用，并讨论了半乳糖凝集素-9在癌症治疗中的潜力以及相关专利。
