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Article: Catalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma
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TitleCatalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma
 
AuthorsChan, KC3
Ko, JMY3
Lung, HL3
Sedlacek, R1
Zhang, ZF4
Luo, DZ4
Feng, ZB4
Chen, S4
Chen, H3
Chan, KW3
Tsao, SW3
Chua, DTT3
Zabarovsky, ER2
Stanbridge, EJ5
Lung, ML3
 
Keywordsangiogenesis
MMP19
nasopharyngeal carcinoma
tumor suppressor gene
 
Issue Date2011
 
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
CitationInternational Journal Of Cancer, 2011, v. 129 n. 8, p. 1826-1837 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25855
 
AbstractThe association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC. Copyright © 2010 UICC.
 
ISSN0020-7136
2013 Impact Factor: 5.007
 
DOIhttp://dx.doi.org/10.1002/ijc.25855
 
ISI Accession Number IDWOS:000294224300004
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChan, KC
 
dc.contributor.authorKo, JMY
 
dc.contributor.authorLung, HL
 
dc.contributor.authorSedlacek, R
 
dc.contributor.authorZhang, ZF
 
dc.contributor.authorLuo, DZ
 
dc.contributor.authorFeng, ZB
 
dc.contributor.authorChen, S
 
dc.contributor.authorChen, H
 
dc.contributor.authorChan, KW
 
dc.contributor.authorTsao, SW
 
dc.contributor.authorChua, DTT
 
dc.contributor.authorZabarovsky, ER
 
dc.contributor.authorStanbridge, EJ
 
dc.contributor.authorLung, ML
 
dc.date.accessioned2011-07-27T01:27:47Z
 
dc.date.available2011-07-27T01:27:47Z
 
dc.date.issued2011
 
dc.description.abstractThe association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC. Copyright © 2010 UICC.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationInternational Journal Of Cancer, 2011, v. 129 n. 8, p. 1826-1837 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25855
 
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.25855
 
dc.identifier.epage1837
 
dc.identifier.hkuros186355
 
dc.identifier.isiWOS:000294224300004
 
dc.identifier.issn0020-7136
2013 Impact Factor: 5.007
 
dc.identifier.issue8
 
dc.identifier.pmid21165953
 
dc.identifier.scopuseid_2-s2.0-80051977695
 
dc.identifier.spage1826
 
dc.identifier.urihttp://hdl.handle.net/10722/135083
 
dc.identifier.volume129
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
dc.publisher.placeUnited States
 
dc.relation.ispartofInternational Journal of Cancer
 
dc.relation.referencesReferences in Scopus
 
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc..
 
dc.subjectangiogenesis
 
dc.subjectMMP19
 
dc.subjectnasopharyngeal carcinoma
 
dc.subjecttumor suppressor gene
 
dc.titleCatalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma
 
dc.typeArticle
 
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<contributor.author>Luo, DZ</contributor.author>
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Author Affiliations
  1. Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic
  2. Karolinska University Hospital
  3. The University of Hong Kong
  4. Guangxi Medical University
  5. UC Irvine