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Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells

https://asahikawa-med.repo.nii.ac.jp/records/144
https://asahikawa-med.repo.nii.ac.jp/records/144
3b8c8cdd-f327-430a-a984-dca112e7a151
名前 / ファイル ライセンス アクション
224.pdf 224.pdf (787.9 kB)
Item type 学術雑誌論文 / Journal Article_02(1)
公開日 2007-02-14
タイトル
タイトル Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells
言語 en
言語
言語 eng
資源タイプ
資源タイプ journal article
著者 水上, 裕輔

× 水上, 裕輔

水上, 裕輔

ja-Kana ミズカミ, ユウスケ

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Jo, WS

× Jo, WS

Jo, WS

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Duerr, EM

× Duerr, EM

Duerr, EM

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Gala, M

× Gala, M

Gala, M

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Li, JN

× Li, JN

Li, JN

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Zhang, XB

× Zhang, XB

Zhang, XB

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Zimmer, MA

× Zimmer, MA

Zimmer, MA

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Iliopoulos, O

× Iliopoulos, O

Iliopoulos, O

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Zukerberg, LR

× Zukerberg, LR

Zukerberg, LR

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Kohgo, Y

× Kohgo, Y

Kohgo, Y

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Lynch, MP

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Lynch, MP

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Rueda, BR

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Rueda, BR

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Chung, DC

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Chung, DC

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著者 ローマ字
Mizukami, Yusuke
出版社 ローマ字
NATURE PUBLISHING GROUP
書誌情報 NATURE MEDICINE

巻 11, 号 9, p. 992-997, 発行日 2005-09-01
ISSN
収録物識別子タイプ ISSN
収録物識別子 1078-8956
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 10.1038/nm1294
リンクURL
内容記述タイプ Other
内容記述 http://www.nature.com/nm/journal/v11/n9/full/nm1294.html | http://www.nature.com/nm/journal/v11/n9/full/nm1294.html
抄録
内容記述タイプ Abstract
内容記述 Hypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis^1, ^2, ^3, ^4. It represents an attractive therapeutic target^5, ^6 in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy^7. But it is unclear whether inhibition of HIF-1 alone is sufficient to block tumor angiogenesis^8, ^9. In HIF-1_α knockdown DLD-1 colon cancer cells (DLD-1^HIF-kd), the hypoxic induction of vascular endothelial growth factor (VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD-1 tumors that had wild-type HIF-1_α (DLD-1^HIF-wt). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin (IL)-8 was induced by hypoxia in DLD-1^HIF-kd but not DLD-1^HIF-wt cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-_KB. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL-8. A neutralizing antibody to IL-8 substantially inhibited angiogenesis and tumor growth in DLD-1^HIF-kd but not DLD-1^HIF-wt xenografts, verifying the functional significance of this IL-8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF-1α may be most effective when IL-8 is simultaneously targeted.
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資源タイプ text
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