Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Miki 761-0793, Japan.
Department of Gastroenterology and Hepatology, Nippon Medical University Hospital, Tokyo 113-8603, Japan.
Int J Mol Sci. 2023 Mar 24;24(7):6174. doi: 10.3390/ijms24076174.
Immunochemotherapy has become popular in recent years. The detailed mechanisms of cancer immunity are being elucidated, and new developments are expected in the future. Apoptosis allows tissues to maintain their form, quantity, and function by eliminating excess or abnormal cells. When apoptosis is inhibited, the balance between cell division and death is disrupted and tissue homeostasis is impaired. This leads to dysfunction and the accumulation of genetically abnormal cells, which can contribute to carcinogenesis. Lectins are neither enzymes nor antibodies but proteins that bind sugar chains. Among soluble endogenous lectins, galectins interact with cell surface sugar chains outside the cell to regulate signal transduction and cell growth. On the other hand, intracellular lectins are present at the plasma membrane and regulate signal transduction by regulating receptor-ligand interactions. Galectin-9 expressed on the surface of thymocytes induces apoptosis of T lymphocytes and plays an essential role in immune self-tolerance by negative selection in the thymus. Furthermore, the administration of extracellular galectin-9 induces apoptosis of human cancer and immunodeficient cells. However, the detailed pharmacokinetics of galectin-9 in vivo have not been elucidated. In addition, the cell surface receptors involved in galectin-9-induced apoptosis of cancer cells have not been identified, and the intracellular pathways involved in apoptosis have not been fully investigated. We have previously reported that galectin-9 induces apoptosis in various gastrointestinal cancers and suppresses tumor growth. However, the mechanism of galectin-9 and apoptosis induction in gastrointestinal cancers and the detailed mechanisms involved in tumor growth inhibition remain unknown. In this article, we review the effects of galectin-9 on gastrointestinal cancers and its mechanisms.
免疫化学疗法近年来变得流行起来。癌症免疫的详细机制正在被阐明，未来预计会有新的发展。细胞凋亡通过消除多余或异常细胞来维持组织的形态、数量和功能。当凋亡受到抑制时，细胞分裂和死亡之间的平衡被打破，组织内稳态受到损害。这导致功能障碍和遗传异常细胞的积累，从而促进致癌作用。凝集素既不是酶也不是抗体，而是结合糖链的蛋白质。在可溶性内源性凝集素中，半乳糖凝集素与细胞外表面的糖链相互作用，调节信号转导和细胞生长。另一方面，细胞内凝集素存在于质膜上，通过调节受体-配体相互作用来调节信号转导。表达在胸腺细胞表面的半乳糖凝集素-9诱导 T 淋巴细胞凋亡，并通过在胸腺中的阴性选择在免疫自我耐受中发挥重要作用。此外，细胞外半乳糖凝集素-9的给药诱导人癌症和免疫缺陷细胞的凋亡。然而，体内半乳糖凝集素-9的详细药代动力学尚未阐明。此外，参与半乳糖凝集素-9诱导癌细胞凋亡的细胞表面受体尚未确定，凋亡涉及的细胞内途径也未被充分研究。我们之前报道过，半乳糖凝集素-9诱导各种胃肠道癌症细胞凋亡并抑制肿瘤生长。然而，半乳糖凝集素-9在胃肠道癌症中诱导凋亡的机制以及肿瘤生长抑制的详细机制仍不清楚。在本文中，我们综述了半乳糖凝集素-9对胃肠道癌症的影响及其机制。
