Article: Glial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells
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- Publisher Website: 10.1016/j.bcp.2010.06.046
- Scopus: eid_2-s2.0-77956226027
- PMID: 20615395
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| Title | Glial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Lu, DY2 Leung, YM2 Cheung, CW1 Chen, YR2 Wong, KL1 3 | ||||||
| Keywords | AP-1 C-Jun GDNF Migration MMP-13 | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm | ||||||
| Citation | Biochemical Pharmacology, 2010, v. 80 n. 8, p. 1201-1209 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bcp.2010.06.046 | ||||||
| Abstract | Malignant gliomas are the most common primary brain tumors in adults and the second most common tumor in children. Gliomas are associated high morbidity and mortality because these tumors are highly invasive into surrounding brain tissue, making complete surgical resection impossible. Glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent neurotrophic factor in a variety of neuronal cell populations. However, the molecular mechanisms and pathologic roles underlying GDNF-induced glioma migration remain unclear. In this study, we found that application of recombinant human GDNF enhances the migration of U87 and U251 cells but not C6 cells. In addition, we found that the expression of matrix metalloproteinase-13 (MMP-13) mRNA, protein and secretion increase in response to GDNF stimulation. The GDNF-induced increase in cell migration was antagonized by MMP-13 neutralizing antibody or silencing MMP-13. We then examined the involvement of mitogen-activated protein kinases (MAPKs) in glioma cell migration induced by GDNF. GDNF-induced MMP-13 expression and glioma migration were attenuated by MEK/extracellular signal-regulating kinase (ERK) and c-Jun N-terminal protein kinase (JNK) inhibitors, as well as ERK and JNK dominant-negative mutants. Treatment with GDNF-induced MEK/ERK and JNK/c-Jun activation and increased AP-1 DNA binding activity in a time-dependent manner. Treatment with AP-1 inhibitors (tanshinone IIA and curcumin) also reduced GDNF-induced glioma cell migration. In migration-prone sublines, cells with greater migration ability had higher GDNF expression. These results indicate that GDNF enhances migration of glioma cells through the increase of MMP-13 production and is mainly regulated by the MEK/ERK and JNK, c-Jun and AP-1 pathways. © 2010 Elsevier Inc. | ||||||
| ISSN | 0006-2952 2011 Impact Factor: 4.705 2011 SCImago Journal Rankings: 0.418 | ||||||
| DOI | http://dx.doi.org/10.1016/j.bcp.2010.06.046 | ||||||
| ISI Accession Number ID | WOS:000281936800010
Funding Information: This work was supported by grants from the National Science Council (NSC 98-2320-B-039-009-MY2 and NSC 98-2627-B-039-005-) and China Medical University (CMU98-N1-29 and CMU98-C-14). | ||||||
| References | References in Scopus |
| dc.contributor.author | Lu, DY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Leung, YM | ||||||
| dc.contributor.author | Cheung, CW | ||||||
| dc.contributor.author | Chen, YR | ||||||
| dc.contributor.author | Wong, KL | ||||||
| dc.date.accessioned | 2011-04-04T02:32:49Z | ||||||
| dc.date.available | 2011-04-04T02:32:49Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Malignant gliomas are the most common primary brain tumors in adults and the second most common tumor in children. Gliomas are associated high morbidity and mortality because these tumors are highly invasive into surrounding brain tissue, making complete surgical resection impossible. Glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent neurotrophic factor in a variety of neuronal cell populations. However, the molecular mechanisms and pathologic roles underlying GDNF-induced glioma migration remain unclear. In this study, we found that application of recombinant human GDNF enhances the migration of U87 and U251 cells but not C6 cells. In addition, we found that the expression of matrix metalloproteinase-13 (MMP-13) mRNA, protein and secretion increase in response to GDNF stimulation. The GDNF-induced increase in cell migration was antagonized by MMP-13 neutralizing antibody or silencing MMP-13. We then examined the involvement of mitogen-activated protein kinases (MAPKs) in glioma cell migration induced by GDNF. GDNF-induced MMP-13 expression and glioma migration were attenuated by MEK/extracellular signal-regulating kinase (ERK) and c-Jun N-terminal protein kinase (JNK) inhibitors, as well as ERK and JNK dominant-negative mutants. Treatment with GDNF-induced MEK/ERK and JNK/c-Jun activation and increased AP-1 DNA binding activity in a time-dependent manner. Treatment with AP-1 inhibitors (tanshinone IIA and curcumin) also reduced GDNF-induced glioma cell migration. In migration-prone sublines, cells with greater migration ability had higher GDNF expression. These results indicate that GDNF enhances migration of glioma cells through the increase of MMP-13 production and is mainly regulated by the MEK/ERK and JNK, c-Jun and AP-1 pathways. © 2010 Elsevier Inc. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Biochemical Pharmacology, 2010, v. 80 n. 8, p. 1201-1209 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.bcp.2010.06.046 | ||||||
| dc.identifier.citeulike | 7480630 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.bcp.2010.06.046 | ||||||
| dc.identifier.epage | 1209 | ||||||
| dc.identifier.hkuros | 183244 | ||||||
| dc.identifier.isi | WOS:000281936800010
Funding Information: This work was supported by grants from the National Science Council (NSC 98-2320-B-039-009-MY2 and NSC 98-2627-B-039-005-) and China Medical University (CMU98-N1-29 and CMU98-C-14). | ||||||
| dc.identifier.issn | 0006-2952 2011 Impact Factor: 4.705 2011 SCImago Journal Rankings: 0.418 | ||||||
| dc.identifier.issue | 8 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 20615395 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77956226027 | ||||||
| dc.identifier.spage | 1201 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/132843 | ||||||
| dc.identifier.volume | 80 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Biochemical Pharmacology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Extracellular Signal-Regulated MAP Kinases - genetics - metabolism | ||||||
| dc.subject.mesh | Gene Expression Regulation, Enzymologic - drug effects | ||||||
| dc.subject.mesh | Glial Cell Line-Derived Neurotrophic Factor - metabolism - pharmacology | ||||||
| dc.subject.mesh | Matrix Metalloproteinase 13 - genetics - metabolism | ||||||
| dc.subject.mesh | Neuroglia - drug effects - physiology | ||||||
| dc.subject | AP-1 | ||||||
| dc.subject | C-Jun | ||||||
| dc.subject | GDNF | ||||||
| dc.subject | Migration | ||||||
| dc.subject | MMP-13 | ||||||
| dc.title | Glial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- null
- China Medical University Hospital Taichung