Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Immunol Res. 2018 Dec;66(6):710-722. doi: 10.1007/s12026-018-9056-x.
Our study demonstrates that (C-X-C motif) ligand 9 and 11 (CXCL9, CXCL11) chemokines were absent basally in non-neoplastic thyroid (TFC) and papillary thyroid carcinoma (PTC) cells. Interferon (IFN)γ induced the chemokine secretion in TFC and PTC, while tumor necrosis factor (TNF)α induced it only in PTC. IFNγ+TNFα induced a synergistic chemokines release in PTC, and at a lower level in TFC. Peroxisome proliferator-activated receptor (PPAR)γ agonists suppressed dose-dependently IFNγ+TNFα-induced chemokine release in TFC, while stimulated it in PTC. PPARγ knocking down, by RNA interference technique in PTC cells, abolished the effect of PPARγ agonists on chemokines release. In PTC cells, PPARγ agonists reduced proliferation, and CXCL9 or CXCL11 (100 and 500 pg/mL) reduced proliferation and migration (P < 0.01, for all). In conclusion, in PTC cells: (a) IFNγ+TNFα induced a marked release of CXCL9 and CXCL11; (b) PPARγ agonists stimulated CXCL9 and CXCL11 secretion, while inhibited proliferation; (c) CXCL9 and CXCL11 inhibited proliferation and migration. The use of CXCL9 or CXCL11 as antineoplastic agents in PTC remains to be explored. HIGHLIGHTS: • IFNγ and IFNγ+TNFα induce dose-dependently CXCL9 (and less CXCL11) in PTC cells. • Rosi and Pio dose-dependently inhibit the PTC cells proliferation. • Rosi and Pio (at variance of normal TFC) stimulate CXCL9 or CXCL11 secretion. • CXCL9 or CXCL11 induce a significant antiproliferative effect in PTC cells. • Chemokines induced by IFNγ (CXCL9 or CXCL11) inhibit migration in PTC cells.
我们的研究表明,(C-X-C 基序)趋化因子 9 和 11(CXCL9、CXCL11)在非肿瘤性甲状腺(TFC)和甲状腺乳头状癌(PTC)细胞中基础水平不存在。干扰素(IFN)γ诱导 TFC 和 PTC 细胞分泌趋化因子,而肿瘤坏死因子(TNF)α仅诱导 PTC 细胞分泌。IFNγ+TNFα 诱导 PTC 细胞协同释放趋化因子,并在较低水平诱导 TFC 细胞释放。过氧化物酶体增殖物激活受体(PPAR)γ激动剂呈剂量依赖性抑制 IFNγ+TNFα诱导的 TFC 趋化因子释放,而刺激 PTC 细胞释放。通过 RNA 干扰技术在 PTC 细胞中敲低 PPARγ,消除了 PPARγ 激动剂对趋化因子释放的影响。在 PTC 细胞中,PPARγ 激动剂降低增殖,而 CXCL9 或 CXCL11(100 和 500 pg/mL)降低增殖和迁移(均 P < 0.01)。总之,在 PTC 细胞中:(a)IFNγ+TNFα 诱导显著释放 CXCL9 和 CXCL11;(b)PPARγ 激动剂刺激 CXCL9 和 CXCL11 分泌,同时抑制增殖;(c)CXCL9 和 CXCL11 抑制增殖和迁移。CXCL9 或 CXCL11 在 PTC 中的抗肿瘤作用有待进一步探讨。要点:•IFNγ 和 IFNγ+TNFα 以剂量依赖方式诱导 PTC 细胞中 CXCL9(和较少的 CXCL11)的产生。•罗西和比奥以剂量依赖方式抑制 PTC 细胞的增殖。•罗西和比奥(与正常 TFC 不同)刺激 CXCL9 或 CXCL11 的分泌。•CXCL9 或 CXCL11 在 PTC 细胞中诱导显著的抗增殖作用。•IFNγ 诱导的趋化因子(CXCL9 或 CXCL11)抑制 PTC 细胞的迁移。