Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Cancer Lett. 2013 Jan 1;328(1):135-43. doi: 10.1016/j.canlet.2012.08.029. Epub 2012 Aug 29.
Osteosarcoma is characterized by a high malignant and metastatic potential. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the effect of IL-6 on migration activity in human osteosarcoma cells is mostly unknown. Here we found that IL-6 increased the migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced IL-6-mediated cell migration. We also found that expression of IL-6 was significantly greater in human osteosarcoma tissues than in normal bone. The integrin-linked kinase (ILK)/Akt/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced expression of ICAM-1 and migration activity was inhibited by the specific inhibitor and siRNA of ILK, Akt, and AP-1 cascades. In addition, over-expression of IL-6 shRNA inhibited the migratory ability and ICAM-1 expression in osteosarcoma cells. Taken together, these results indicate that IL-6 and IL-6 receptor interaction occurs through ILK and Akt, which in turn activates AP-1, resulting in the activations of ICAM-1 and contributing the migration of human osteosarcoma cells.
骨肉瘤的特点是恶性程度高，转移性强。白细胞介素-6（IL-6）是一种多功能细胞因子，与癌症的疾病状态和转归有关。然而，IL-6 对人骨肉瘤细胞迁移活性的影响大多尚不清楚。在这里，我们发现 IL-6 增加了人骨肉瘤细胞的迁移和细胞间黏附分子-1（ICAM-1）的表达。ICAM-1 siRNA 转染细胞可降低 IL-6 介导的细胞迁移。我们还发现，人骨肉瘤组织中 IL-6 的表达明显高于正常骨。IL-6 处理后，整合素连接激酶（ILK）/Akt/AP-1 通路被激活，ILK、Akt 和 AP-1 级联的特异性抑制剂和 siRNA 抑制了 IL-6 诱导的 ICAM-1 表达和迁移活性。此外，过表达 IL-6 shRNA 抑制了骨肉瘤细胞的迁移能力和 ICAM-1 的表达。综上所述，这些结果表明，IL-6 和 IL-6 受体通过 ILK 和 Akt 相互作用，进而激活 AP-1，导致 ICAM-1 的激活，并促进人骨肉瘤细胞的迁移。
