| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2007-02-14 |
| タイトル |
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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 |
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|
言語 |
eng |
| 資源タイプ |
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資源タイプ |
journal article |
| 著者 |
水上, 裕輔
Jo, WS
Duerr, EM
Gala, M
Li, JN
Zhang, XB
Zimmer, MA
Iliopoulos, O
Zukerberg, LR
Kohgo, Y
Lynch, MP
Rueda, BR
Chung, DC
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| 著者 ローマ字 |
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Mizukami, Yusuke |
| 出版社 ローマ字 |
|
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NATURE PUBLISHING GROUP |
| 書誌情報 |
NATURE MEDICINE
巻 11,
号 9,
p. 992-997,
発行日 2005-09-01
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1078-8956 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
10.1038/nm1294 |
| リンクURL |
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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 |
|
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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. |
| 注記 |
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内容記述タイプ |
Other |
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注記 |
author |
| 資源タイプ |
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内容記述タイプ |
Other |
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資源タイプ |
text |
| 著者版フラグ |
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出版タイプ |
AM |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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16127434 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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1893 |
224.pdf (787.9 kB)
