title: β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
abstract: Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Lin
authors.forename: Hui-Jye
authors.initials: HJ
authors.lastname: Chen
authors.forename: Te-Mao
authors.initials: TM
authors.lastname: Li
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.forename: Shan-Chi
authors.initials: SC
authors.lastname: Liu
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chen
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002813:Chondrosarcoma / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D039641:Integrin beta Chains; D016328:NF-kappa B; C084344:integrin beta5; D019869:Phosphatidylinositol 3-Kinases; D020813:Receptor, trkB; D051057:Proto-Oncogene Proteins c-akt