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
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-09-4510
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).

PubMed Central IDPMC2896444
ReferencesReferences in Scopus
DC Field
Value
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.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
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
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
Author Affiliations
  1. Karolinska University Hospital
  2. The University of Hong Kong
  3. Hong Kong Polytechnic University
  4. UC Irvine
  5. Cleveland Clinic Foundation