Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Biochem Soc Trans. 2022 Feb 28;50(1):135-149. doi: 10.1042/BST20200677.
Galectin-8 (Gal-8) belongs to a family of animal lectins that modulate cell adhesion, cell proliferation, apoptosis, and immune responses. Recent studies have shown that mammalian Gal-8 induces in an autocrine and paracrine manner, the expression and secretion of cytokines and chemokines such as RANKL, IL-6, IL-1β, SDF-1, and MCP-1. This involves Gal-8 binding to receptor complexes that include MRC2/uPAR/LRP1, integrins, and CD44. Receptors ligation triggers FAK, ERK, Akt, and the JNK signaling pathways, leading to induction of NF-κB that promotes cytokine expression. Indeed, immune-competent Gal-8 knockout (KO) mice express systemic lower levels of cytokines and chemokines while the opposite is true for Gal-8 transgenic animals. Cytokine and chemokine secretion, induced by Gal-8, promotes the migration of cancer cells toward cells expressing this lectin. Accordingly, Gal-8 KO mice experience reduced tumor size and smaller and fewer metastatic lesions when injected with cancer cells. These observations suggest the existence of a 'vicious cycle' whereby Gal-8 expression and secretion promotes the secretion of cytokines and chemokines that further promote Gal-8 expression. This 'vicious cycle' could enhance the development of a 'cytokine storm' which is a key contributor to the poor prognosis of COVID-19 patients.
半乳糖凝集素-8（Gal-8）属于动物凝集素家族，可调节细胞黏附、细胞增殖、凋亡和免疫反应。最近的研究表明，哺乳动物 Gal-8 通过自分泌和旁分泌方式诱导细胞因子和趋化因子的表达和分泌，如 RANKL、IL-6、IL-1β、SDF-1 和 MCP-1。这涉及 Gal-8 与包含 MRC2/uPAR/LRP1、整合素和 CD44 的受体复合物结合。受体的连接触发 FAK、ERK、Akt 和 JNK 信号通路，导致 NF-κB 的诱导，从而促进细胞因子的表达。事实上，免疫功能正常的 Gal-8 敲除（KO）小鼠表达系统性较低水平的细胞因子和趋化因子，而 Gal-8 转基因动物则相反。Gal-8 诱导的细胞因子和趋化因子的分泌促进癌细胞向表达这种凝集素的细胞迁移。因此，当用癌细胞注射时，Gal-8 KO 小鼠的肿瘤体积减小，转移灶更小、更少。这些观察结果表明存在一个“恶性循环”，即 Gal-8 的表达和分泌促进细胞因子和趋化因子的分泌，进一步促进 Gal-8 的表达。这个“恶性循环”可能会增强“细胞因子风暴”的发展，这是 COVID-19 患者预后不良的一个关键因素。
