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Article: Extracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis

TitleExtracellular protease ADAMTS9 suppresses esophageal and nasopharyngeal carcinoma tumor formation by inhibiting angiogenesis
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2010, v. 70 n. 13, p. 5567-5576 How to Cite?
Abstract
ADAMTS 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.
Persistent Identifierhttp://hdl.handle.net/10722/90487
ISSN
2013 Impact Factor: 9.284
2013 SCImago Journal Rankings: 5.627
PubMed Central ID
ISI Accession Number ID
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).

References

 

Author Affiliations
  1. Karolinska University Hospital
  2. The University of Hong Kong
  3. Hong Kong Polytechnic University
  4. UC Irvine
  5. Cleveland Clinic Foundation
DC FieldValueLanguage
dc.contributor.authorLo, PHYen_HK
dc.contributor.authorLung, HLen_HK
dc.contributor.authorCheung, AKLen_HK
dc.contributor.authorApte, SSen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorKwong, FMen_HK
dc.contributor.authorKo, JMYen_HK
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorLaw, Sen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorZabarovsky, ERen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorTang, JCOen_HK
dc.contributor.authorStanbridge, EJen_HK
dc.contributor.authorLung, MLen_HK
dc.date.accessioned2010-09-10T06:19:34Z-
dc.date.available2010-09-10T06:19:34Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Research, 2010, v. 70 n. 13, p. 5567-5576en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90487-
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.en_HK
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
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 angiogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=70&issue=13&spage=5567&epage=5576&date=2010&atitle=Extracellular+protease+ADAMTS9+suppresses+esophageal+and+nasopharyngeal+carcinoma+tumor+formation+by+inhibiting+angiogenesis-
dc.identifier.emailLung, HL: hllung2@hku.hken_HK
dc.identifier.emailCheung, AKL: arthurhk@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hkucc.hku.hken_HK
dc.identifier.emailCheng, Y: yuecheng@hku.hken_HK
dc.identifier.emailLaw, S: slaw@hkucc.hku.hken_HK
dc.identifier.emailSrivastava, G: gopesh@pathology.hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hkucc.hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hken_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityCheung, AKL=rp01769en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityCheng, Y=rp01320en_HK
dc.identifier.authorityLaw, S=rp00437en_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-09-4510en_HK
dc.identifier.pmid20551050en_HK
dc.identifier.pmcidPMC2896444-
dc.identifier.scopuseid_2-s2.0-77954352573en_HK
dc.identifier.hkuros170952-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954352573&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue13en_HK
dc.identifier.spage5567en_HK
dc.identifier.epage5576en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000279396800039-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLo, PHY=36762664000en_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridCheung, AKL=8967932600en_HK
dc.identifier.scopusauthoridApte, SS=7101907193en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridKwong, FM=8158557800en_HK
dc.identifier.scopusauthoridKo, JMY=35725559400en_HK
dc.identifier.scopusauthoridCheng, Y=36131038300en_HK
dc.identifier.scopusauthoridLaw, S=7202241293en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK
dc.identifier.scopusauthoridZabarovsky, ER=7007009108en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridTang, JCO=14056850300en_HK
dc.identifier.scopusauthoridStanbridge, EJ=7103249410en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK

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