IL-6 promotes ICAM-1 expression and cell motility in human
osteosarcoma
Yi-Chin Fong 1,2,3, Chih-Hsin Tang 4,5
1. School of Chinese Medicine, China Medical University, Taichung, Taiwan
2. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan 3. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan 4. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan 5. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
Abstrate
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.
