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Article: Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis
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TitleExtracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis
 
AuthorsLo, PHY2
Lung, HL2
Cheung, AKL2
Apte, SS5
Chan, KW2
Kwong, FM2
Ko, JMY2
Cheng, Y2
Law, S2
Srivastava, G2
Zabarovsky, ER1
Tsao, SW2
Tang, JCO2 3
Stanbridge, EJ4
Lung, ML2
 
Issue Date2010
 
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
CitationCancer Research, 2010, v. 70 n. 13, p. 5567-5576 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-09-4510
 
AbstractADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we evaluated the hypothesized antiangiogenic and tumor-suppressive functions of ADAMTS9 in ESCC and NPC, in stringent tumorigenicity and Matrigel plug angiogenesis assays. ADAMTS9 activation suppressed tumor formation in nude mice. Conversely, knockdown of ADAMTS9 resulted in clones reverting to the tumorigenic phenotype of parental cells. In vivo angiogenesis assays revealed a reduction in microvessel numbers in gel plugs injected with tumor-suppressive cell transfectants. Similarly, conditioned medium from cell transfectants dramatically reduced the tube-forming capacity of human umbilical vein endothelial cells. These activities were associated with a reduction in expression levels of the proangiogenic factors MMP9 and VEGFA, which were consistently reduced in ADAMTS9 transfectants derived from both cancers. Taken together, our results indicate that ADAMTS9 contributes an important function in the tumor microenvironment that acts to inhibit angiogenesis and tumor growth in both ESCC and NPC. ©2010 AACR.
 
ISSN0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-09-4510
 
PubMed Central IDPMC2896444
 
ISI Accession Number IDWOS:000279396800039
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of ChinaHKU6617/08M
HKU6415/06M
NIHAR49930
Swedish Cancer Society
Swedish Research Council
Swedish Institute
Cancer Research Institute in New York/Concern Foundation in Los Angeles
Karolinska Institute
Funding Information:

Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China: grants HKU6617/08M and HKU6415/06M (M. L. Lung); NIH award AR49930 (S. S. Apte); and Swedish Cancer Society, Swedish Research Council, Swedish Institute, Cancer Research Institute in New York/Concern Foundation in Los Angeles, and Karolinska Institute (E. R. Zabarovsky).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLo, PHY
 
dc.contributor.authorLung, HL
 
dc.contributor.authorCheung, AKL
 
dc.contributor.authorApte, SS
 
dc.contributor.authorChan, KW
 
dc.contributor.authorKwong, FM
 
dc.contributor.authorKo, JMY
 
dc.contributor.authorCheng, Y
 
dc.contributor.authorLaw, S
 
dc.contributor.authorSrivastava, G
 
dc.contributor.authorZabarovsky, ER
 
dc.contributor.authorTsao, SW
 
dc.contributor.authorTang, JCO
 
dc.contributor.authorStanbridge, EJ
 
dc.contributor.authorLung, ML
 
dc.date.accessioned2010-09-10T06:19:34Z
 
dc.date.available2010-09-10T06:19:34Z
 
dc.date.issued2010
 
dc.description.abstractADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we evaluated the hypothesized antiangiogenic and tumor-suppressive functions of ADAMTS9 in ESCC and NPC, in stringent tumorigenicity and Matrigel plug angiogenesis assays. ADAMTS9 activation suppressed tumor formation in nude mice. Conversely, knockdown of ADAMTS9 resulted in clones reverting to the tumorigenic phenotype of parental cells. In vivo angiogenesis assays revealed a reduction in microvessel numbers in gel plugs injected with tumor-suppressive cell transfectants. Similarly, conditioned medium from cell transfectants dramatically reduced the tube-forming capacity of human umbilical vein endothelial cells. These activities were associated with a reduction in expression levels of the proangiogenic factors MMP9 and VEGFA, which were consistently reduced in ADAMTS9 transfectants derived from both cancers. Taken together, our results indicate that ADAMTS9 contributes an important function in the tumor microenvironment that acts to inhibit angiogenesis and tumor growth in both ESCC and NPC. ©2010 AACR.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationCancer Research, 2010, v. 70 n. 13, p. 5567-5576 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-09-4510
 
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-09-4510
 
dc.identifier.eissn1538-7445
 
dc.identifier.epage5576
 
dc.identifier.hkuros170952
 
dc.identifier.isiWOS:000279396800039
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of ChinaHKU6617/08M
HKU6415/06M
NIHAR49930
Swedish Cancer Society
Swedish Research Council
Swedish Institute
Cancer Research Institute in New York/Concern Foundation in Los Angeles
Karolinska Institute
Funding Information:

Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China: grants HKU6617/08M and HKU6415/06M (M. L. Lung); NIH award AR49930 (S. S. Apte); and Swedish Cancer Society, Swedish Research Council, Swedish Institute, Cancer Research Institute in New York/Concern Foundation in Los Angeles, and Karolinska Institute (E. R. Zabarovsky).

 
dc.identifier.issn0008-5472
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
 
dc.identifier.issue13
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2896444
 
dc.identifier.pmid20551050
 
dc.identifier.scopuseid_2-s2.0-77954352573
 
dc.identifier.spage5567
 
dc.identifier.urihttp://hdl.handle.net/10722/90487
 
dc.identifier.volume70
 
dc.languageeng
 
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofCancer Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshADAM Proteins - biosynthesis - genetics - metabolism
 
dc.subject.meshEndothelial Cells - cytology
 
dc.subject.meshEnzyme Activation
 
dc.subject.meshEsophageal Neoplasms - blood supply - enzymology - genetics
 
dc.subject.meshNasopharyngeal Neoplasms - blood supply - enzymology - genetics
 
dc.titleExtracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis
 
dc.typeArticle
 
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Author Affiliations
  1. Karolinska University Hospital
  2. The University of Hong Kong
  3. Hong Kong Polytechnic University
  4. UC Irvine
  5. Cleveland Clinic Foundation