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Abstract：
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.
摘要：
我们的研究表明，（C-X-C基序）配体9和11（CXCL9，CXCL11）趋化因子在非肿瘤性甲状腺（TFC）和乳头状甲状腺癌（PTC）细胞中基本不存在。干扰素（IFN）γ诱导TFC和PTC中趋化因子的分泌，而肿瘤坏死因子（TNF）α仅在PTC中诱导。IFNγ+TNFα诱导PTC协同释放趋化因子，在TFC中处于较低水平。过氧化物酶体增殖物激活受体(PPAR)γ激动剂剂量依赖性抑制IFNγ+TNFα诱导的TFC趋化因子释放,同时在PTC中刺激它。PPARγ击倒,通过RNA干扰技术在PTC细胞中，取消了PPARγ激动剂对趋化因子释放的影响。在PTC电池中,PPARγ激动剂减少增殖，和CXCL9或CXCL11(100和500μg/mL)减少增殖和迁移(P<0.01,全部)。总之,在PTC细胞中:(a)IFNγ+TNFα诱导CXCL9和CXCL11的显著释放;(b)PPARγ激动剂刺激CXCL9和CXCL11的分泌,同时抑制增殖；（c）CXCL9和CXCL11抑制增殖和迁移。CXCL9或CXCL11在PTC中作为抗肿瘤剂的用途仍有待探索。突出:·IFNγ和IFNγ+TNFα在PTC细胞中剂量依赖性地诱导CXCL9(和更少的CXCL11)。•Rosi和Pio剂量依赖性地抑制PTC细胞增殖。•Rosi和Pio(在正常TFC的变化下)刺激CXCL9或CXCL11分泌。•CXCL9或CXCL11在PTC细胞中诱导显著的抗增殖作用。•由IFNγ(CXCL9或CXCL11)诱导的趋化因子抑制PTC细胞中的迁移。
