title: Apoptosis signal-regulating kinase 1 is involved in brain-derived neurotrophic factor (BDNF)-enhanced cell motility and matrix metalloproteinase 1 expression in human chondrosarcoma cells.
abstract: Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. p123400@hotmail.com
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Lin
authors.forename: Sunny Li-Yun
authors.initials: SL
authors.lastname: Chang
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.forename: Chin-Jung
authors.initials: CJ
authors.lastname: Hsu
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013879:Thioredoxins / Q000494:pharmacology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000873:Anthracenes; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D007093:Imidazoles; D026121:Indole Alkaloids; D011725:Pyridines; C432165:pyrazolanthrone; D013879:Thioredoxins; C579455:BDNF protein, human; C049985:staurosporine aglycone; D011494:Protein Kinases; C065999:Sp1 kinase; D020813:Receptor, trkB; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C093642:SB 203580
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