Department of Endocrinology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of Geriatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
J Clin Endocrinol Metab. 2020 Aug 1;105(8). doi: 10.1210/clinem/dgaa344.
Myeloid-derived suppressor cells (MDSCs) have become increasingly recognized as facilitators of tumor development. However, the role of MDSCs in papillary thyroid carcinoma (PTC) progression has not been clearly explored.
We aimed to evaluate the levels and function of circulating MDSCs in PTC.
The proportion of circulating polymorphonuclear (PMN)-MDSCs and mononuclear-MDSCs from patients with PTC or benign thyroid nodules and healthy controls was measured using flow cytometry. For immunosuppressive activity analysis, sorted circulating MDSCs were cocultured with CD3/CD28-costimulated T lymphocytes and the proliferation of T cells was determined. PTC cell lines (TPC-1 and BC-PAP) were cocultured with PMN-MDSCs, and the effects on cell migration, invasion, proliferation, and apoptosis were evaluated. The differential expressed microribonucleic acids (RNAs) and messenger RNAs and their function were also explored in TPC-1 cells cocultured with or without PMN-MDSCs.
PMN-MDSCs were increased in peripheral blood mononuclear cells of patients with PTC. Circulating PMN-MDSCs displayed strong T cell suppressive activity. PTC cells demonstrated enhanced invasive capabilities in vitro and in vivo when cocultured with sorted PMN-MDSCs. PMN-MDSCs decreased expression of miR-486-3p and activated nuclear factor kappa B2 (NF-κB2), a direct target of miR-486-3p. Rescue of miR-486-3p diminished the cell migration and invasion induced by PMN-MDSCs.
Collectively, our work indicates that circulating PMN-MDSCs promote PTC progression. By suppressing miR-486-3p, PMN-MDSCs promote the activity of the NF-κB2 signaling pathway, resulting in accelerated invasion of PTC cells, which may provide new therapeutic strategies for treatment of thyroid cancer.
髓系来源的抑制细胞（MDSCs）已被越来越多地认为是肿瘤发展的促进因素。然而，MDSCs 在甲状腺乳头状癌（PTC）进展中的作用尚未得到明确探讨。
我们旨在评估循环 MDSCs 在 PTC 中的水平和功能。
采用流式细胞术测量来自 PTC 或良性甲状腺结节患者及健康对照者的循环多形核（PMN）-MDSCs 和单核-MDSCs 的比例。为了进行免疫抑制活性分析，将分选的循环 MDSCs 与 CD3/CD28 共刺激 T 淋巴细胞共培养，并测定 T 细胞的增殖。将 PTC 细胞系（TPC-1 和 BC-PAP）与 PMN-MDSCs 共培养，评估对细胞迁移、侵袭、增殖和凋亡的影响。还在 TPC-1 细胞与或不与 PMN-MDSCs 共培养的情况下，探索差异表达的微核糖核酸（miRNAs）和信使 RNA 及其功能。
PTC 患者外周血单个核细胞中 PMN-MDSCs 增加。循环 PMN-MDSCs 具有强大的 T 细胞抑制活性。当与分选的 PMN-MDSCs 共培养时，PTC 细胞在体外和体内显示出增强的侵袭能力。PMN-MDSCs 降低了 miR-486-3p 的表达并激活了核因子 kappa B2（NF-κB2），miR-486-3p 的直接靶标。恢复 miR-486-3p 可减弱 PMN-MDSCs 诱导的细胞迁移和侵袭。
综上所述，我们的工作表明，循环 PMN-MDSCs 促进 PTC 进展。PMN-MDSCs 通过抑制 miR-486-3p 促进 NF-κB2 信号通路的活性，导致 PTC 细胞侵袭加速，这可能为甲状腺癌的治疗提供新的治疗策略。
