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Article: Glial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells

TitleGlial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells
Authors
KeywordsAP-1
C-Jun
GDNF
Migration
MMP-13
Issue Date2010
PublisherElsevier 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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/132843
ISSN
2013 Impact Factor: 4.650
2013 SCImago Journal Rankings: 1.994
ISI Accession Number ID
Funding AgencyGrant Number
National Science CouncilNSC 98-2320-B-039-009-MY2
NSC 98-2627-B-039-005-
China Medical UniversityCMU98-N1-29
CMU98-C-14
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

 

DC FieldValueLanguage
dc.contributor.authorLu, DYen_HK
dc.contributor.authorLeung, YMen_HK
dc.contributor.authorCheung, CWen_HK
dc.contributor.authorChen, YRen_HK
dc.contributor.authorWong, KLen_HK
dc.date.accessioned2011-04-04T02:32:49Z-
dc.date.available2011-04-04T02:32:49Z-
dc.date.issued2010en_HK
dc.identifier.citationBiochemical Pharmacology, 2010, v. 80 n. 8, p. 1201-1209en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132843-
dc.description.abstractMalignant 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.en_HK
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.subjectAP-1en_HK
dc.subjectC-Junen_HK
dc.subjectGDNFen_HK
dc.subjectMigrationen_HK
dc.subjectMMP-13en_HK
dc.subject.meshExtracellular Signal-Regulated MAP Kinases - genetics - metabolism-
dc.subject.meshGene Expression Regulation, Enzymologic - drug effects-
dc.subject.meshGlial Cell Line-Derived Neurotrophic Factor - metabolism - pharmacology-
dc.subject.meshMatrix Metalloproteinase 13 - genetics - metabolism-
dc.subject.meshNeuroglia - drug effects - physiology-
dc.titleGlial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=80&issue=8&spage=1201&epage=1209&date=2010&atitle=Glial+cell+line-derived+neurotrophic+factor+induces+cell+migration+and+matrix+metalloproteinase-13+expression+in+glioma+cells-
dc.identifier.emailCheung, CW:cheucw@hku.hken_HK
dc.identifier.authorityCheung, CW=rp00244en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2010.06.046en_HK
dc.identifier.pmid20615395en_HK
dc.identifier.scopuseid_2-s2.0-77956226027en_HK
dc.identifier.hkuros183244-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956226027&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume80en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1201en_HK
dc.identifier.epage1209en_HK
dc.identifier.isiWOS:000281936800010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike7480630-

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