Osteopontin increases migration and MMP‐9 up‐regulation via αvβ3 integrin,FAK, ERK,and NF‐κB‐dependent pathway in human chondrosarcoma cells |
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| Authors: | Ying‐Ju Chen Ying‐Ying Wei Hsien‐Te Chen Yi‐Chin Fong Chin‐Jung Hsu Chun‐Hao Tsai Horng‐Chaung Hsu Shing‐Hwa Liu Chih‐Hsin Tang |
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| Institution: | 1. School of Pharmacy, China Medical University, Taichung, Taiwan;2. Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan;3. School of Cosmeceutics, China Medical University, Taichung, Taiwan;4. Department of Orthopaedic, China Medical University Hospital, Taichung, Taiwan;5. School of Chinese Medicine, China Medical University, Taichung, Taiwan;6. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;7. Department of Pharmacology, China Medical University, Taichung, Taiwan |
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| Abstract: | Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and proliferation via interaction with its receptor, that is, αvβ3 integrin. However, the effect of OPN on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that OPN increased the migration and expression of matrix metalloproteinase (MMP)‐9 in human chondrosarcoma cells (JJ012 cells). RGD peptide, αvβ3 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the OPN‐induced increase of the migration and MMP‐9 up‐regulation of chondrosarcoma cells. OPN stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal‐regulated kinase (ERK). In addition, treatment of JJ012 cells with NF‐κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) inhibited OPN‐induced cell migration and MMP‐9 up‐regulation. Stimulation of JJ012 cells with OPN also induced IκB kinase α/β (IKK α/β) phosphorylation, IκBα phosphorylation, p65 Ser536 phosphorylation, and κB‐luciferase activity. The OPN‐mediated increases in MMP‐9 and κB‐luciferase activities were inhibited by RGD peptide, PD98059 or FAK and ERK2 mutant. Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP‐9 expression through the αvβ3 integrin, FAK, MEK, ERK and NF‐κB signal transduction pathway. J. Cell. Physiol. 221: 98–108, 2009. © 2009 Wiley‐Liss, Inc |
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