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Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells
https://asahikawa-med.repo.nii.ac.jp/records/3863
https://asahikawa-med.repo.nii.ac.jp/records/3863cad3622a-ade3-4ae5-bb19-ad5efb401417
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
4574.pdf (1.7 MB)
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| Item type | 学術雑誌論文 / Journal Article_02(1) | |||||||||||||||||||||||||||||||||||
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| 公開日 | 2012-05-30 | |||||||||||||||||||||||||||||||||||
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| タイトル | Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells | |||||||||||||||||||||||||||||||||||
| 言語 | en | |||||||||||||||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||||||||||||||
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| 資源タイプ | journal article | |||||||||||||||||||||||||||||||||||
| 著者 |
中村, 和正
× 中村, 和正
× Sasajima, Junpei
× Mizukami, Yusuke
× Sugiyama, Yoshiaki
× Yamazaki, Madoka
× Fujii, Rie
× Kawamoto, Toru
× Koizumi, Kazuya
× Sato, Kazuya
× Fujiya, Mikihiro
× Sasaki, Katsunori
× Tanno, Satoshi
× Okumura, Toshikatsu
× Shimizu, Norihiko
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| 書誌情報 |
PloS one 巻 5, 号 1, p. e8824-1-e8824-11, 発行日 2010-01-01 |
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| 収録物識別子タイプ | EISSN | |||||||||||||||||||||||||||||||||||
| 収録物識別子 | 1932-6203 | |||||||||||||||||||||||||||||||||||
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| 関連タイプ | isIdenticalTo | |||||||||||||||||||||||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||||||||||||||||||||||
| 関連識別子 | 10.1371/journal.pone.0008824 | |||||||||||||||||||||||||||||||||||
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| 内容記述タイプ | Abstract | |||||||||||||||||||||||||||||||||||
| 内容記述 | Background: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells. Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity. Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis. | |||||||||||||||||||||||||||||||||||
| 言語 | en | |||||||||||||||||||||||||||||||||||
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| 内容記述タイプ | Other | |||||||||||||||||||||||||||||||||||
| 注記 | http://creativecommons.org/licenses/by/2.0/ Publisher | |||||||||||||||||||||||||||||||||||
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| 内容記述タイプ | Other | |||||||||||||||||||||||||||||||||||
| 資源タイプ | text | |||||||||||||||||||||||||||||||||||
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| 出版タイプ | VoR | |||||||||||||||||||||||||||||||||||
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| 内容記述タイプ | Other | |||||||||||||||||||||||||||||||||||
| 内容記述 | application/pdf | |||||||||||||||||||||||||||||||||||
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| 8312 | ||||||||||||||||||||||||||||||||||||
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| 808 | ||||||||||||||||||||||||||||||||||||
