Zhang You-Yuan, Liu Ze-Bing, Ye Xuan-Guang, Ren Wei-Min
Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
Mol Med Rep. 2016 Oct;14(4):3941-6. doi: 10.3892/mmr.2016.5686. Epub 2016 Aug 29.
Treatment with high iodine concentrations can delay oncogenic activation effects, reduce cell growth and return thyroid-specific gene and protein expression levels to normal. During rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) 3 activation, excess iodine can act as a protective agent in thyroid follicular cells. The chemokine receptor CCR7 serves a critical role in lymphocyte trafficking into and within lymph nodes, the preferential metastatic site for PTC. However, the potential associations between chemokine (C‑C motif) ligand 21 (CCL21)/C‑C chemokine receptor type 7 (CCR7) interaction and iodine concentrations in primary cultures of PTC with RET/PTC expression remain unclear. Proliferation assays of primary cultures of PTC cells with RET/PTC1 and RET/PTC3 expression indicated that CCR7 activation by its specific ligand, CCL21, was associated with significantly increased cell proliferation. Flow cytometry data indicated that CCL21/CCR7 interaction significantly increased the fraction of cells in the G2/M phase of the cell cycle. Western blotting indicated that CCL21/CCR7 interaction significantly upregulated cyclin A, cyclin B1 and cyclin‑dependent kinase 1 (CDK1) expression. Western blotting determined that CCL21/CCR7 interaction significantly enhanced the levels of phosphorylated extracellular signal‑regulated kinase (P‑ERK). Co-immunoprecipitation confirmed that there was interaction between P‑ERK and cyclin A, cyclin B1 or CDK1, particularly in the presence of CCL21. Sodium iodide (NaI, 10-5 M) significantly abolished the effects of exogenous CCL21. These results suggest that CCL21/CCR7 interaction contributes to G2/M progression of RET/PTC‑expressing cells via the ERK pathway in association with 10‑5 M NaI.
高碘浓度治疗可延迟致癌激活效应，减少细胞生长，并使甲状腺特异性基因和蛋白质表达水平恢复正常。在转染重排（RET）/甲状腺乳头状癌（PTC）3激活过程中，过量碘可作为甲状腺滤泡细胞中的保护剂。趋化因子受体CCR7在淋巴细胞进入和在淋巴结内运输中起关键作用，而淋巴结是PTC的优先转移部位。然而，在具有RET/PTC表达的PTC原代培养物中，趋化因子（C-C基序）配体21（CCL21）/C-C趋化因子受体7型（CCR7）相互作用与碘浓度之间的潜在关联仍不清楚。对具有RET/PTC1和RET/PTC3表达的PTC细胞原代培养物进行增殖分析表明，其特异性配体CCL21激活CCR7与细胞增殖显著增加相关。流式细胞术数据表明，CCL21/CCR7相互作用显著增加了细胞周期G2/M期的细胞比例。蛋白质印迹法表明，CCL21/CCR7相互作用显著上调细胞周期蛋白A、细胞周期蛋白B1和细胞周期蛋白依赖性激酶1（CDK1）的表达。蛋白质印迹法确定，CCL21/CCR7相互作用显著增强磷酸化细胞外信号调节激酶（P-ERK）的水平。免疫共沉淀证实P-ERK与细胞周期蛋白A、细胞周期蛋白B1或CDK1之间存在相互作用，特别是在存在CCL21的情况下。碘化钠（NaI，10-5 M）显著消除了外源性CCL21的作用。这些结果表明，CCL21/CCR7相互作用通过ERK途径与10-5 M NaI相关，促进了表达RET/PTC的细胞的G2/M期进程。
