Laboratorio de Investigación Aplicada en Neurociencias (LIAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Belén de Escobar B1625, Argentina.
Laboratorio de Glicomedicina, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1428, Argentina.
Int J Mol Sci. 2021 Dec 28;23(1):316. doi: 10.3390/ijms23010316.
Despite recent advances in diagnosis and treatment, glioblastoma (GBM) represents the most common and aggressive brain tumor in the adult population, urging identification of new rational therapeutic targets. Galectins, a family of glycan-binding proteins, are highly expressed in the tumor microenvironment (TME) and delineate prognosis and clinical outcome in patients with GBM. These endogenous lectins play key roles in different hallmarks of cancer by modulating tumor cell proliferation, oncogenic signaling, migration, vascularization and immunity. Additionally, they have emerged as mediators of resistance to different anticancer treatments, including chemotherapy, radiotherapy, immunotherapy, and antiangiogenic therapy. Particularly in GBM, galectins control tumor cell transformation and proliferation, reprogram tumor cell migration and invasion, promote vascularization, modulate cell death pathways, and shape the tumor-immune landscape by targeting myeloid, natural killer (NK), and CD8 T cell compartments. Here, we discuss the role of galectins, particularly galectin-1, -3, -8, and -9, as emerging glyco-checkpoints that control different mechanisms associated with GBM progression, and discuss possible therapeutic opportunities based on inhibition of galectin-driven circuits, either alone or in combination with other treatment modalities.
尽管在诊断和治疗方面取得了最近的进展，但胶质母细胞瘤（GBM）仍是成人中最常见和侵袭性最强的脑肿瘤，迫切需要确定新的合理治疗靶点。半乳糖凝集素是一类糖结合蛋白家族，在肿瘤微环境（TME）中高度表达，并可预测 GBM 患者的预后和临床结果。这些内源性凝集素通过调节肿瘤细胞增殖、致癌信号、迁移、血管生成和免疫，在癌症的不同特征中发挥关键作用。此外，它们已成为对包括化疗、放疗、免疫治疗和抗血管生成治疗在内的不同抗癌治疗产生耐药性的介质。特别是在 GBM 中，半乳糖凝集素控制肿瘤细胞的转化和增殖，重新编程肿瘤细胞的迁移和侵袭，促进血管生成，调节细胞死亡途径，并通过靶向髓样细胞、自然杀伤（NK）细胞和 CD8 T 细胞来塑造肿瘤免疫景观。在这里，我们讨论了半乳糖凝集素（特别是半乳糖凝集素-1、-3、-8 和-9）作为新兴的糖检查点的作用，这些检查点控制与 GBM 进展相关的不同机制，并讨论了基于抑制半乳糖凝集素驱动的回路的可能治疗机会，无论是单独使用还是与其他治疗方式联合使用。
