Wang Li-Na, Cui Yu-Xin, Ruge Fiona, Jiang Wen G
Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K. Immunology Research Group, Weifang Medical University, Weifang, Shandong, P.R. China.
Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff, U.K.
Cancer Genomics Proteomics. 2015 Sep-Oct;12(5):211-21.
Interleukin 21 (IL21) is a cytokine produced predominantly by cluster of differentiation 4 (CD4+) T-cells and natural killer T-cells. There exists evidence that IL21 is implicated in various immunological processes through its specific receptor (IL21R). However, the participation of IL21 in the pathogenesis of solid tumors is not fully conclusive. In the present study, we demonstrated that there was differential expression of IL21R in breast cancer cells using reverse transcription-polymerase chain reaction (RT-PCR), western blotting and sequence analysis. The expression of IL21R was stronger in MDA-231 cells, weaker in MCF7 but negative in ZR-75.1 cells. The invasion and migratory capacity of IL21R+ MDA-231 cells was enhanced by IL21 in a dose-dependent manner. After IL21R was knocked-down by siRNA gene silencing, the response of MDA-231 to treatment with IL21 was attenuated. We found that siRNA silencing of IL21R also spontaneously suppressed cell proliferation. However, IL21 had no additional effect on the proliferation of MDA-231 cells. We also found that IL21R was involved in signaling pathways of matrix metalloproteinases (MMPs), that are crucial for spreading and migration of metastatic MDA231 cells. In conclusion, we unveiled the roles of IL21R in breast cancer cells, which enhances our knowledge on immunological regulation of cancer cells through the axis of IL21 and its receptor.
白细胞介素21（IL21）是一种主要由分化簇4（CD4+）T细胞和自然杀伤T细胞产生的细胞因子。有证据表明，IL21通过其特异性受体（IL21R）参与各种免疫过程。然而，IL21在实体瘤发病机制中的参与情况尚未完全明确。在本研究中，我们使用逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法和序列分析证明，乳腺癌细胞中IL21R存在差异表达。IL21R在MDA-231细胞中的表达较强，在MCF7细胞中较弱，而在ZR-75.1细胞中为阴性。IL21以剂量依赖的方式增强了IL21R+ MDA-231细胞的侵袭和迁移能力。在用小干扰RNA（siRNA）基因沉默敲低IL21R后，MDA-231对IL21治疗的反应减弱。我们发现，siRNA沉默IL21R也会自发抑制细胞增殖。然而，IL21对MDA-231细胞的增殖没有额外影响。我们还发现，IL21R参与了基质金属蛋白酶（MMPs）的信号通路，而基质金属蛋白酶对于转移性MDA231细胞的扩散和迁移至关重要。总之，我们揭示了IL21R在乳腺癌细胞中的作用，这增强了我们对通过IL21及其受体轴对癌细胞进行免疫调节的认识。
