Involvement of Integrin Up-Regulation in RANKL/RANK Pathway of Chondrosarcomas Migration

invasion of tumor cells is the primary cause of therapeutic failure in malignant chondrosarcomas treatment Receptor activator of nuclear factor-kappa B 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 Mat RANKL directed the migration and increased cell surface expression of [31 integrin in human chondrosarcoma cells (11012 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-kappa B inhibitor (PDTC) or I kappa B 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 IKK alpha/beta and NF-kappa B, resulting in the activation of beta 1 integrin and contributing to the migration of human chondrosarcoma cells J Cell Biochem 111 138-147, 2010 (C) 2010 Wilcy-Liss. Inc