School of Chinese Medicine, China Medical University, Taichung, Taiwan.
J Cell Biochem. 2012 Nov;113(11):3353-62. doi: 10.1002/jcb.24211.
Interleukin-11 (IL-11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL-11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL-11 on human chondrosarcoma cells are largely unknown. Here, we found that IL-11 increased the migration and expression of intercellular adhesion molecule-1 (ICAM)-1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL-11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways were activated by IL-11 treatment, and the IL-11-induced expression of ICAM-1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF-κB cascades. Taken together, our results indicate that IL-11 enhanced the migration of the chondrosarcoma cells by increasing ICAM-1 expression through the IL-11Rα receptor, PI3K, Akt, and NF-κB signal transduction pathway.
白细胞介素-11（IL-11）最初被鉴定为能够诱导人类细胞增殖的细胞因子。最近的研究表明，IL-11 在肿瘤生长、血管生成和转移中发挥着关键作用。软骨肉瘤是一种高度恶性的肿瘤，具有很强的局部侵袭和远处转移的能力。然而，IL-11 对人软骨肉瘤细胞的影响在很大程度上是未知的。在这里，我们发现 IL-11 增加了人软骨肉瘤细胞的迁移和细胞间黏附分子-1（ICAM-1）的表达。我们还发现人软骨肉瘤组织中 IL-11 的表达明显高于原代软骨细胞。IL-11 处理激活了磷脂酰肌醇 3-激酶（PI3K）、Akt 和 NF-κB 通路，并且 PI3K、Akt 和 NF-κB 级联的特异性抑制剂和突变形式抑制了 IL-11 诱导的 ICAM-1 表达和迁移活性。总之，我们的结果表明，IL-11 通过 IL-11Rα 受体、PI3K、Akt 和 NF-κB 信号转导通路增加 ICAM-1 的表达，从而增强了软骨肉瘤细胞的迁移。
