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
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
DOIhttp://dx.doi.org/10.1002/ijc.25855
ReferencesReferences in Scopus
DC Field
Value
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.issn0020-7136
2011 Impact Factor: 5.444
2011 SCImago Journal Rankings: 0.620
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
Author Affiliations
  1. null
  2. Karolinska University Hospital
  3. The University of Hong Kong
  4. Guangxi Medical University
  5. UC Irvine