PDF(Pubmed)
Abstract：
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 Ca2+, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca2+ 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.
摘要：
自然杀伤（NK）细胞可以快速迁移到肿瘤部位，对肿瘤产生细胞毒作用，还有一些趋化因子,包括CXCL8、CXCL10或CXCL12,都可以调控NK细胞的迁移。激活素A,转化生长因子β（TGF-β）超家族的成员，在肿瘤组织中高表达，参与肿瘤的发展和免疫细胞的活化。在这项研究中,我们关注激活素A对NK细胞迁移的影响。体外，激活素A诱导NK细胞迁移和侵袭，促进细胞极化，抑制细胞粘附。此外，激活素A增加Ca2+，NK细胞中p-SMAD3和p-AKT水平。AKT抑制剂和Ca2+螯合剂部分阻断活化素A诱导的NK细胞迁移。在体内,外源性激活素A增加NS-1细胞实体瘤中肿瘤浸润NK细胞并抑制肿瘤生长,在4T-1细胞实体瘤中，用抗激活素A抗体阻断内源性激活素A可减少肿瘤浸润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的NK细胞来增强NK细胞的抗肿瘤作用。
