title: Visfatin triggers the in vitro migration of osteosarcoma cells via activation of NF-κB/IL-6 signals.
abstract: Pulmonary metastasis is the major challenge for clinical treatment of osteosarcoma patients. Recent studies indicated that visfatin, a 52kDa adipocytokine, can trigger the cell motility of various cancers, while its role in the progression of osteosarcoma remains not clear. Our present study revealed that visfatin can significantly promote the in vitro migration and invasion of osteosarcoma MG-63 and HOS cells and up regulate the expression of matrix metalloproteinase-2 (MMP-2) and fibronectin (FN). Furthermore, visfatin treatment also increased the expression of IL-6 in both MG-63 and HOS cells via a time dependent manner, while anti-IL-6 antibody can significantly attenuate visfatin induced cell invasion and up regulation of MMP-2 and FN. It suggested that up regulation of IL-6 mediated visfatin induced in vitro motility of osteosarcoma cells. Visfatin treatment can increase the phosphorylation of both p65 and ERK1/2 in MG-63 and HOS cells, while only the inhibitor of NF-κB, BAY 11-7082, can abolish visfatin induced up regulation of IL-6. BAY 11-7082 also attenuated visfatin induced upregulation of MMP-2 and FN in MG-63 cells. Western blot analysis revealed that visfatin treatment can significantly increase the phosphorylation of IκBα and IKKβ in MG-63 cells. ACHP, the inhibitor of IKK-β, blocked visfatin induced expression of IL-6 mRNA in both MG-63 and HOS cells. Collectively, our data suggested that visfatin can increase the motility of osteosarcoma cells via up regulation of NF-κB/IL-6 signals. It indicated that visfatin might be a potential therapeutic target of osteosarcoma treatment.
authors: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China; Department of joint surgery, Hainan General Hospital, Haikou, 570311 Hainan, China.
authors: Guang-Ji
authors: GJ
authors: Wang
authors: Department of joint surgery, Hainan General Hospital, Haikou, 570311 Hainan, China.
authors: Ning-Jiang
authors: NJ
authors: Shen
authors: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
authors: Liang
authors: L
authors: Cheng
authors: Department of joint surgery, Hainan General Hospital, Haikou, 570311 Hainan, China.
authors: Yehan Fang
authors: Department of joint surgery, Hainan General Hospital, Haikou, 570311 Hainan, China.
authors: Hui
authors: H
authors: Huang
authors: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China. Electronic address: likanghuacs@163.com.
authors: Kang-Hua
authors: KH
authors: Li
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D012516:Osteosarcoma / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005353:Fibronectins; D015850:Interleukin-6; D016328:NF-kappa B; D000072000:NF-KappaB Inhibitor alpha; D054409:Nicotinamide Phosphoribosyltransferase; D051550:I-kappa B Kinase; D020778:Matrix Metalloproteinase 2
keywords: IL-6; Migration; NF-κB; Osteosarcoma; Visfatin