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Article: Brain-derived neurotrophic factor promotes tumorigenesis via induction of neovascularization: Implication in hepatocellular carcinoma
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TitleBrain-derived neurotrophic factor promotes tumorigenesis via induction of neovascularization: Implication in hepatocellular carcinoma
 
AuthorsLam, CT1
Yang, ZF1 1
Lau, CK1
Tam, KH1
Fan, ST1 1
Poon, RTP1 1
 
KeywordsBrain derived neurotrophic factor
Angiogenesis
Animal cell
Cell invasion
Cell migration
 
Issue Date2011
 
PublisherAmerican Association for Cancer Research.
 
CitationClinical Cancer Research, 2011, v. 17 n. 10, p. 3123-3133 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-10-2802
 
AbstractPurpose: Brain-derived neurotrophic factor (BDNF) has emerged as a novel angiogenic factor, and yet its impact on tumorigenesis is unclear. This study aimed at investigating the roles of BDNF in angiogenesis and tumor development. Experimental Design: BDNF was overexpressed in a mouse endothelial cell (EC) line by stable transfection, and angiogenic properties of the transfectants were assessed. Microarray analysis was employed to explore the molecular pathways. The impact of modulating BDNF levels in two mouse EC lines on tumorigenic potential of a transformed mouse liver cell line was evaluated by an in vivo cotransplantation model. BDNF and tropomyosin receptor kinase B (TrkB) protein levels were determined in 50 pairs of human hepatocellular carcinoma (HCC) tissues by Western blotting and immunohistochemistry. Survival analysis was carried out to determine their clinical significance. Results: Overexpression of BDNF could promote EC proliferation, migration, invasion, and survival. Microarray and molecular studies showed that RhoA, caspase-9, caspase-3, growth arrest specific 6, and VEGF could mediate BDNF/TrkB-induced angiogenesis. The cotransplantation experiment showed that high BDNF-expressing ECs could facilitate tumor angiogenesis and growth, whereas knockdown of BDNF by short hairpin RNAs impaired such effects. Furthermore, examination on human HCC tissues revealed upregulation of BDNF and TrkB protein levels in 46.0% and 33.3% of the cases studied, respectively. Immunohistochemistry disclosed strong BDNF reactivity in both tumor and endothelial cells. High TrkB expression was associated with shorter overall survival. Conclusions: BDNF/TrkB system was crucial for tumor angiogenesis and growth, which may represent a potential target for antiangiogenic therapy in HCC. ©2011 AACR.
 
ISSN1078-0432
2012 Impact Factor: 7.837
2012 SCImago Journal Rankings: 3.798
 
DOIhttp://dx.doi.org/10.1158/1078-0432.CCR-10-2802
 
ISI Accession Number IDWOS:000290610000008
Funding AgencyGrant Number
University of Hong Kong
Research Grant Council Hong KongHKU5/CRF/08
Funding Information:

This study was supported by Small Project Funding of the University of Hong Kong and by the Collaborative Research Fund (HKU5/CRF/08) of the Research Grant Council Hong Kong.

 
ReferencesReferences in Scopus
 
GrantsLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury
 
DC FieldValue
dc.contributor.authorLam, CT
 
dc.contributor.authorYang, ZF
 
dc.contributor.authorLau, CK
 
dc.contributor.authorTam, KH
 
dc.contributor.authorFan, ST
 
dc.contributor.authorPoon, RTP
 
dc.date.accessioned2011-07-27T01:36:44Z
 
dc.date.available2011-07-27T01:36:44Z
 
dc.date.issued2011
 
dc.description.abstractPurpose: Brain-derived neurotrophic factor (BDNF) has emerged as a novel angiogenic factor, and yet its impact on tumorigenesis is unclear. This study aimed at investigating the roles of BDNF in angiogenesis and tumor development. Experimental Design: BDNF was overexpressed in a mouse endothelial cell (EC) line by stable transfection, and angiogenic properties of the transfectants were assessed. Microarray analysis was employed to explore the molecular pathways. The impact of modulating BDNF levels in two mouse EC lines on tumorigenic potential of a transformed mouse liver cell line was evaluated by an in vivo cotransplantation model. BDNF and tropomyosin receptor kinase B (TrkB) protein levels were determined in 50 pairs of human hepatocellular carcinoma (HCC) tissues by Western blotting and immunohistochemistry. Survival analysis was carried out to determine their clinical significance. Results: Overexpression of BDNF could promote EC proliferation, migration, invasion, and survival. Microarray and molecular studies showed that RhoA, caspase-9, caspase-3, growth arrest specific 6, and VEGF could mediate BDNF/TrkB-induced angiogenesis. The cotransplantation experiment showed that high BDNF-expressing ECs could facilitate tumor angiogenesis and growth, whereas knockdown of BDNF by short hairpin RNAs impaired such effects. Furthermore, examination on human HCC tissues revealed upregulation of BDNF and TrkB protein levels in 46.0% and 33.3% of the cases studied, respectively. Immunohistochemistry disclosed strong BDNF reactivity in both tumor and endothelial cells. High TrkB expression was associated with shorter overall survival. Conclusions: BDNF/TrkB system was crucial for tumor angiogenesis and growth, which may represent a potential target for antiangiogenic therapy in HCC. ©2011 AACR.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationClinical Cancer Research, 2011, v. 17 n. 10, p. 3123-3133 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-10-2802
 
dc.identifier.doihttp://dx.doi.org/10.1158/1078-0432.CCR-10-2802
 
dc.identifier.epage3133
 
dc.identifier.hkuros187636
 
dc.identifier.isiWOS:000290610000008
Funding AgencyGrant Number
University of Hong Kong
Research Grant Council Hong KongHKU5/CRF/08
Funding Information:

This study was supported by Small Project Funding of the University of Hong Kong and by the Collaborative Research Fund (HKU5/CRF/08) of the Research Grant Council Hong Kong.

 
dc.identifier.issn1078-0432
2012 Impact Factor: 7.837
2012 SCImago Journal Rankings: 3.798
 
dc.identifier.issue10
 
dc.identifier.openurl
 
dc.identifier.pmid21421859
 
dc.identifier.scopuseid_2-s2.0-79955990588
 
dc.identifier.spage3123
 
dc.identifier.urihttp://hdl.handle.net/10722/135540
 
dc.identifier.volume17
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research.
 
dc.publisher.placeUnited States
 
dc.relation.ispartofClinical Cancer Research
 
dc.relation.projectLiver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBrain derived neurotrophic factor
 
dc.subjectAngiogenesis
 
dc.subjectAnimal cell
 
dc.subjectCell invasion
 
dc.subjectCell migration
 
dc.titleBrain-derived neurotrophic factor promotes tumorigenesis via induction of neovascularization: Implication in hepatocellular carcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong