BMP-7 enhances cell migration and αvβ3 integrin expression via a c-Src-dependent pathway in human chondrosarcoma cells.
Bone morphogenic protein (BMP)-7 is a member of the transforming growth factor (TGF)-beta superfamily, which is originally identified based on its ability to induce cartilage and bone formation. In recent years, BMP-7 is also defined as a potent promoter of cell motility, invasion, and metastasis. However, there is little knowledge of the role of BMP-7 and its cellular function in chondrosarcoma cells. In the present study, we investigated the biological impact of BMP-7 on cell motility using transwell assay. In addition, the intracellular signaling pathways were also investigated by pharmacological and genetic approaches. Our results demonstrated that treatment with exogenous BMP-7 markedly increased cell migration by activating c-Src/PI3K/Akt/IKK/NF-κB signaling pathway, resulting in the transactivation of αvβ3 integrin expression. Indeed, abrogation of signaling activation, by chemical inhibition or expression of a kinase dead form of the protein attenuated BMP-7-induced expression of integrin αvβ3 and cell migration. These findings may provide a useful tool for diagnostic/prognostic purposes and even therapeutically in late-stage chondrosarcoma as an anti-metastatic agent.
Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan.
Jui-Chieh
JC
Chen
School of Pharmacy, China Medical University, Taichung, Taiwan.
Shu-Ting
ST
Yang
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Chih-Yang
CY
Lin
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Chin-Jung
CJ
Hsu
Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan; Department of Medicine and Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Chun-Hao
CH
Tsai
National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
Jen-Liang
JL
Su
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
Chih-Hsin
CH
Tang
D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002813:Chondrosarcoma / Q000378:metabolism*; D016391:Genes, src / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D055419:Bone Morphogenetic Protein 7; D039302:Integrin alphaVbeta3; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt