β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.

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...

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Autores principales: Chih-Yang Lin, Hui-Jye Chen, Te-Mao Li, Yi-Chin Fong, Shan-Chi Liu, Po-Chun Chen, Chih-Hsin Tang
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/9c836448b2aa4ed9bb452ac5ef42a01e
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spelling oai:doaj.org-article:9c836448b2aa4ed9bb452ac5ef42a01e2021-11-18T07:38:12Zβ5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.1932-620310.1371/journal.pone.0067990https://doaj.org/article/9c836448b2aa4ed9bb452ac5ef42a01e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874483/?tool=EBIhttps://doaj.org/toc/1932-6203Chondrosarcoma 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.Chih-Yang LinHui-Jye ChenTe-Mao LiYi-Chin FongShan-Chi LiuPo-Chun ChenChih-Hsin TangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67990 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chih-Yang Lin
Hui-Jye Chen
Te-Mao Li
Yi-Chin Fong
Shan-Chi Liu
Po-Chun Chen
Chih-Hsin Tang
β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
description 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.
format article
author Chih-Yang Lin
Hui-Jye Chen
Te-Mao Li
Yi-Chin Fong
Shan-Chi Liu
Po-Chun Chen
Chih-Hsin Tang
author_facet Chih-Yang Lin
Hui-Jye Chen
Te-Mao Li
Yi-Chin Fong
Shan-Chi Liu
Po-Chun Chen
Chih-Hsin Tang
author_sort Chih-Yang Lin
title β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
title_short β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
title_full β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
title_fullStr β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
title_full_unstemmed β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
title_sort β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/9c836448b2aa4ed9bb452ac5ef42a01e
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