Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Key Laboratory of Neuroimmunology and Clinical Immunology, Changchun 130021, China.
Cells. 2024 Apr 23;13(9):728. doi: 10.3390/cells13090728.
Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor β (TGF-β) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of activin A on NK cell migration. In vitro, activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, activin A increased Ca, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that activin A induces NK cell migration through AKT signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.
自然杀伤 (NK) 细胞可以迅速迁移到肿瘤部位，对肿瘤发挥细胞毒性作用，一些趋化因子，如 CXCL8、CXCL10 或 CXCL12，可以调节 NK 细胞的迁移。激活素 A 是转化生长因子 β (TGF-β) 超家族的成员，在肿瘤组织中高度表达，参与肿瘤的发生和免疫细胞的激活。在本研究中，我们重点研究了激活素 A 对 NK 细胞迁移的影响。在体外，激活素 A 诱导 NK 细胞迁移和侵袭，促进细胞极化并抑制细胞黏附。此外，激活素 A 增加了 NK 细胞中的 Ca、p-SMAD3 和 p-AKT 水平。AKT 抑制剂和 Ca 螯合剂部分阻断了激活素 A 诱导的 NK 细胞迁移。在体内，外源性激活素 A 增加了 NS-1 细胞实体瘤中的肿瘤浸润性 NK 细胞并抑制了肿瘤生长，而用抗激活素 A 抗体阻断内源性激活素 A 则减少了 4T-1 细胞实体瘤中的肿瘤浸润性 NK 细胞。这些结果表明，激活素 A 通过 AKT 信号和钙信号诱导 NK 细胞迁移，并可能通过增加肿瘤浸润性 NK 细胞来增强 NK 细胞的抗肿瘤作用。
