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Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin
DC Field | Value | Language |
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dc.contributor.author | Adachi, Yasushi | - |
dc.contributor.author | Li, Rong | - |
dc.contributor.author | Yamamoto, Hiroyuki | - |
dc.contributor.author | Min, Yongfen | - |
dc.contributor.author | Wang, Yu | - |
dc.contributor.author | Li, Hua | - |
dc.contributor.author | Lee, Choon-Taek | - |
dc.contributor.author | Carbone, David P. | - |
dc.contributor.author | Shinomura, Yasuhisa | - |
dc.contributor.author | Imai, Kohzoh | - |
dc.contributor.author | Arimura, Yoshiaki | - |
dc.contributor.author | Imsumran, Arisa | - |
dc.contributor.author | Piao, Wenhua | - |
dc.date.accessioned | 2012-06-26T00:52:34Z | - |
dc.date.available | 2012-06-26T00:52:34Z | - |
dc.date.issued | 2009-08 | - |
dc.identifier.citation | CARCINOGENESIS; Vol.30 8; 1305-1313 | ko_KR |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77415 | - |
dc.description.abstract | Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. We have previously shown significant therapeutic activity for recombinant adenoviruses expressing dominant-negative insulin-like growth factor-I receptor (IGF-IR/dn), including suppression of tumor invasion. In this study, we sought to evaluate the mechanism of inhibition of invasion and the relationship between IGF-IR and matrix metalloproteinase (MMP) activity in GI carcinomas. We analyzed the role of IGF-IR on invasion in three GI cancer cell lines, colorectal adenocarcinoma, HT29; pancreatic adenocarcinoma, BxPC3 and gastric adenocarcinoma, MKN45, using a modified Boyden chamber method and subcutaneous xenografts in nude mice. The impact of IGF-IR signaling on the expression of MMPs and the effects of blockade of matrilysin or IGF-IR on invasiveness were assessed using recombinant adenoviruses, a tyrosine kinase inhibitor NVP-AEW541 and antisense matrilysin. Invasive subcutaneous tumors expressed several MMPs. IGF-IR/dn reduced the expression of these MMPs but especially matrilysin (MMP-7). Insulin-like growth factor (IGF) stimulated secretion of matrilysin and IGF-IR/dn blocked IGF-mediated matrilysin induction in three GI cancers. Both IGF-IR/dn and inhibition of matrilysin reduced in vitro invasion to the same degree. NVP-AEW541 also reduced cancer cell invasion both in vitro and in murine xenograft tumors via suppression of matrilysin. Thus, blockade of IGF-IR is involved in the suppression of cancer cell invasion through downregulation of matrilysin. Strategies of targeting IGF-IR may have significant therapeutic utility to prevent invasion and progression of human GI carcinomas. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | OXFORD UNIV PRESS | ko_KR |
dc.title | Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 이춘택 | - |
dc.identifier.doi | 10.1093/carcin/bgp134 | - |
dc.citation.journaltitle | CARCINOGENESIS | - |
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dc.description.tc | 9 | - |
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