Involvement of integrin up-regulation in RANKL/RANK pathway of chondrosarcomas migration

✍ Scribed by Chin-Jung Hsu; Tsang-Yu Lin; Chien-Chung Kuo; Chun-Hao Tsai; Mou-Zen Lin; Horng-Chaung Hsu; Yi-Chin Fong; Chih-Hsin Tang

• Book ID: 102303766
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 345 KB
• Volume: 111
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22677

✦ Synopsis

Abstract

Invasion of tumor cells is the primary cause of therapeutic failure in malignant chondrosarcomas treatment. Receptor activator of nuclear factor‐κB ligand (RANKL) and its receptor, RANK, play a key roles in osteoclastogenesis and tumor metastasis. We found that the RANKL and RANK expression in human chondrosarcoma tissues was higher than that in normal cartilage. We also found that RANKL directed the migration and increased cell surface expression of β1 integrin in human chondrosarcoma cells (JJ012 cells). Pretreatment of JJ012 cells with MAPK kinase (MEK) inhibitors, PD98059 or U0126, inhibited the RANKL‐induced migration and integrin expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal‐regulating kinase (ERK). In addition, NF‐κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited RANKL‐induced cells migration and integrin up‐regulation. Taken together, these results suggest that the RANKL acts through MEK/ERK, which in turn activates IKKα/β and NF‐κB, resulting in the activation of β1 integrin and contributing to the migration of human chondrosarcoma cells. J. Cell. Biochem. 111: 138–147, 2010. © 2010 Wiley‐Liss, Inc.