Cited 35 times in
Combined targeting of high-mobility group box-1 and interleukin-8 to control micrometastasis potential in gastric cancer
DC Field | Value | Language |
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dc.contributor.author | 김호근 | - |
dc.contributor.author | 임종백 | - |
dc.contributor.author | 장선필 | - |
dc.contributor.author | 정혜원 | - |
dc.date.accessioned | 2016-02-04T11:48:19Z | - |
dc.date.available | 2016-02-04T11:48:19Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0020-7136 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/141242 | - |
dc.description.abstract | Micrometastasis is the major cause of treatment failure in gastric cancer (GC). Because epithelial-to-mesenchymal transition (EMT) is considered to develop prior to macroscopic metastasis, EMT-promoting factors may affect micrometastasis. This study aimed to evaluate the role of extracellular high-mobility group box-1 (HMGB1) in EMT and the treatment effect of combined targeting of HMGB1 and interleukin-8 (IL-8) at early-stage GC progression through interrupting EMT promotion. Extracellular HMGB1 was induced by human recombinant HMGB1 and pCMV-SPORT6-HMGB1 plasmid transfection. EMT activation was evaluated by immunoblotting, immunofluorescence and immunohistochemistry. Increased migration/invasion activities were evaluated by in vitro transwell migration/invasion assay using all histological types of human GC cell lines (N87, MKN28 SNU-1 and KATOIII), N87-xenograft BALB/c nude mice and human paired serum-tissue GC samples. HMGB1-induced soluble factors were measured by chemiluminescent immunoassay. Inhibition effects of tumor growth and EMT activation by combined targeting of HMGB1 and IL-8 were evaluated in N87-xenograft nude mice. Serum HMGB1 increases along the GC carcinogenesis and reaches maximum before macroscopic metastasis. Overexpressed extracellular HMGB1 promoted EMT activation and increased cell motility/invasiveness through ligation to receptor for advanced glycation end products. HMGB1-induced IL-8 overexpression contributed the HMGB1-induced EMT in GC in vitro and in vivo. Blocking HMGB1 caused significant reduction of tumor growth, and addition of human recombinant IL-8 rescues this antitumor effects. Our results imply the role of HMGB1 in EMT through IL-8 mediation, and a potential mechanism of GC micrometastasis. Our observations suggest combination strategy of HMGB1 and IL-8 as a promising diagnostic and therapeutic target to control GC micrometastasis. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1598~1609 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF CANCER | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Combined targeting of high-mobility group box-1 and interleukin-8 to control micrometastasis potential in gastric cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학) | - |
dc.contributor.googleauthor | Hye Won Chung | - |
dc.contributor.googleauthor | Sunphil Jang | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.contributor.googleauthor | Jong-Baeck Lim | - |
dc.identifier.doi | 10.1002/ijc.29539 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01183 | - |
dc.contributor.localId | A03403 | - |
dc.contributor.localId | A03782 | - |
dc.contributor.localId | A03433 | - |
dc.relation.journalcode | J01092 | - |
dc.identifier.eissn | 1097-0215 | - |
dc.identifier.url | http://onlinelibrary.wiley.com/doi/10.1002/ijc.29539/abstract | - |
dc.subject.keyword | HMGB1 | - |
dc.subject.keyword | IL-8 | - |
dc.subject.keyword | EMT | - |
dc.subject.keyword | gastric cancer | - |
dc.subject.keyword | metastasis | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.alternativeName | Lim, Jong Baeck | - |
dc.contributor.alternativeName | Jang, Sun Phil | - |
dc.contributor.alternativeName | Chung, Hye Won | - |
dc.contributor.affiliatedAuthor | Kim, Ho Keun | - |
dc.contributor.affiliatedAuthor | Lim, Jong Baeck | - |
dc.contributor.affiliatedAuthor | Chung, Hye Won | - |
dc.contributor.affiliatedAuthor | Jang, Sun Phil | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 137 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1598 | - |
dc.citation.endPage | 1609 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF CANCER, Vol.137(7) : 1598-1609, 2015 | - |
dc.identifier.rimsid | 31433 | - |
dc.type.rims | ART | - |
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