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The effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression.

DC FieldValueLanguage
dc.contributor.author김정민-
dc.contributor.author라선영-
dc.contributor.author박승우-
dc.contributor.author신유근-
dc.contributor.author유은정-
dc.contributor.author장향란-
dc.contributor.author정현철-
dc.contributor.author정희철-
dc.date.accessioned2015-12-28T10:56:42Z-
dc.date.available2015-12-28T10:56:42Z-
dc.date.issued2014-
dc.identifier.issn1535-7163-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/138361-
dc.description.abstractAdvanced gastric cancer is one of the most aggressive gastrointestinal malignancies, and ADAM (A disintegrin and metalloproteinase)-9 is a cell-surface membrane glycoprotein with oncogenic properties that is overexpressed in several cancers. Herein, we investigated the biologic mechanism of ADAM9 in the progression, proliferation, and invasion of gastric cancer. First, we detected ADAM's expression, processing, and protease activity in gastric cancer cells. Protease activity was moderately correlated with ADAM9 protein expression, but was better related to a processed smaller molecular weight (84 kDa) form of ADAM9. Knockdown of ADAM9 or specifically targeted monoclonal antibody (RAV-18) suppressed cancer cell proliferation and invasion in high ADAM9-expressing cells, not in low ADAM9-expressing cells. RAV-18 showed in vivo antitumor activity in a gastric cancer xenograft model. Hypoxia (1% oxygen) induced ADAM9 expression and functional activity in low ADAM9-expressing gastric cancer cells that was inhibited by siRNA knockdown or RAV-18 antibody to levels in normoxic cells. Overall, our studies show that ADAM9 plays an important role in gastric cancer proliferation and invasion, and that while expressed in some gastric cancer cells at high levels that are responsive to functional inhibition and antitumor activity of a catalytic site-directed antibody, other gastric cancer cells have low levels of expression and only when exposed to hypoxia do ADAM9 levels increase and the cells become responsive to ADAM9 antibody inhibition. Therefore, our findings suggest that ADAM9 could be an effective therapeutic target for advanced gastric cancer.-
dc.description.statementOfResponsibilityopen-
dc.format.extent3074~3085-
dc.relation.isPartOfMolecular Cancer Therapeutics-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHADAM Proteins/antagonists & inhibitors-
dc.subject.MESHADAM Proteins/genetics-
dc.subject.MESHADAM Proteins/metabolism*-
dc.subject.MESHAnimals-
dc.subject.MESHAntibodies, Monoclonal/administration & dosage-
dc.subject.MESHAntibodies, Monoclonal/pharmacology-
dc.subject.MESHAntineoplastic Agents/administration & dosage-
dc.subject.MESHAntineoplastic Agents/pharmacology-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Movement-
dc.subject.MESHCell Proliferation-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDisease Progression-
dc.subject.MESHDisintegrins/metabolism*-
dc.subject.MESHEnzyme Activation-
dc.subject.MESHFemale-
dc.subject.MESHGene Expression-
dc.subject.MESHGene Expression Profiling-
dc.subject.MESHHeterografts-
dc.subject.MESHHumans-
dc.subject.MESHHypoxia/metabolism-
dc.subject.MESHMembrane Proteins/antagonists & inhibitors-
dc.subject.MESHMembrane Proteins/genetics-
dc.subject.MESHMembrane Proteins/metabolism*-
dc.subject.MESHMice-
dc.subject.MESHNeoplasm Invasiveness-
dc.subject.MESHProtein Binding-
dc.subject.MESHRNA Interference-
dc.subject.MESHStomach Neoplasms/drug therapy-
dc.subject.MESHStomach Neoplasms/genetics-
dc.subject.MESHStomach Neoplasms/metabolism*-
dc.subject.MESHStomach Neoplasms/pathology*-
dc.subject.MESHTumor Burden/drug effects-
dc.titleThe effect of disintegrin-metalloproteinase ADAM9 in gastric cancer progression.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorJeong Min Kim-
dc.contributor.googleauthorHei Cheul Jeung-
dc.contributor.googleauthorSun Young Rha-
dc.contributor.googleauthorEun Jeong Yu-
dc.contributor.googleauthorTae Soo Kim-
dc.contributor.googleauthorYou Keun Shin-
dc.contributor.googleauthorXianglan Zhang-
dc.contributor.googleauthorKyu Hyun Park-
dc.contributor.googleauthorSeung Woo Park-
dc.contributor.googleauthorHyun Cheol Chung-
dc.contributor.googleauthorGarth Powis-
dc.identifier.doi10.1158/1535-7163.MCT-13-1001-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01551-
dc.contributor.localIdA02127-
dc.contributor.localIdA02491-
dc.contributor.localIdA03489-
dc.contributor.localIdA03773-
dc.contributor.localIdA00886-
dc.contributor.localIdA03794-
dc.contributor.localIdA01316-
dc.relation.journalcodeJ02254-
dc.identifier.pmid25344581-
dc.identifier.urlhttp://mct.aacrjournals.org/content/13/12/3074-
dc.contributor.alternativeNameKim, Jung Min-
dc.contributor.alternativeNameRha, Sun Young-
dc.contributor.alternativeNamePark, Seung Woo-
dc.contributor.alternativeNameShin, You Keun-
dc.contributor.alternativeNameYu, Eun Jeong-
dc.contributor.alternativeNameZhang, Xiang Lan-
dc.contributor.alternativeNameChung, Hyun Cheol-
dc.contributor.alternativeNameJeung, Hei Cheul-
dc.contributor.affiliatedAuthorPark, Seung Woo-
dc.contributor.affiliatedAuthorShin, You Keun-
dc.contributor.affiliatedAuthorYu, Eun Jeong-
dc.contributor.affiliatedAuthorZhang, Xiang Lan-
dc.contributor.affiliatedAuthorChung, Hyun Cheol-
dc.contributor.affiliatedAuthorKim, Jung Min-
dc.contributor.affiliatedAuthorJeung, Hei Cheul-
dc.contributor.affiliatedAuthorRha, Sun Young-
dc.rights.accessRightsfree-
dc.citation.volume13-
dc.citation.number12-
dc.citation.startPage3074-
dc.citation.endPage3085-
dc.identifier.bibliographicCitationMolecular Cancer Therapeutics, Vol.13(12) : 3074-3085, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers

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