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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis

http://hdl.handle.net/2237/00031508
http://hdl.handle.net/2237/00031508
6e33ee24-6365-473a-a59b-e1c5a89c8d9f
名前 / ファイル ライセンス アクション
Mizutani_et_al_for_repository.pdf Mizutani_et_al_for_repository (12.5 MB)
Mizutani_et_al_Suppl_Data.pdf Mizutani_et_al_Suppl_Data (20.8 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2020-02-14
タイトル
タイトル Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis
言語 en
著者 Mizutani, Yasuyuki

× Mizutani, Yasuyuki

WEKO 96038

en Mizutani, Yasuyuki

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Kobayashi, Hiroki

× Kobayashi, Hiroki

WEKO 96039

en Kobayashi, Hiroki

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Iida, Tadashi

× Iida, Tadashi

WEKO 96040

en Iida, Tadashi

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Asai, Naoya

× Asai, Naoya

WEKO 96041

en Asai, Naoya

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Masamune, Atsushi

× Masamune, Atsushi

WEKO 96042

en Masamune, Atsushi

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Hara, Akitoshi

× Hara, Akitoshi

WEKO 96043

en Hara, Akitoshi

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Esaki, Nobutoshi

× Esaki, Nobutoshi

WEKO 96044

en Esaki, Nobutoshi

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Ushida, Kaori

× Ushida, Kaori

WEKO 96045

en Ushida, Kaori

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Mii, Shinji

× Mii, Shinji

WEKO 96046

en Mii, Shinji

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Shiraki, Yukihiro

× Shiraki, Yukihiro

WEKO 96047

en Shiraki, Yukihiro

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Ando, Kenju

× Ando, Kenju

WEKO 96048

en Ando, Kenju

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Weng, Liang

× Weng, Liang

WEKO 96049

en Weng, Liang

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Ishihara, Seiichiro

× Ishihara, Seiichiro

WEKO 96050

en Ishihara, Seiichiro

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Ponik, Suzanne M.

× Ponik, Suzanne M.

WEKO 96051

en Ponik, Suzanne M.

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Conklin, Matthew W.

× Conklin, Matthew W.

WEKO 96052

en Conklin, Matthew W.

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Haga, Hisashi

× Haga, Hisashi

WEKO 96053

en Haga, Hisashi

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Nagasaka, Arata

× Nagasaka, Arata

WEKO 96054

en Nagasaka, Arata

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Miyata, Takaki

× Miyata, Takaki

WEKO 96055

en Miyata, Takaki

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Matsuyama, Makoto

× Matsuyama, Makoto

WEKO 96056

en Matsuyama, Makoto

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Kobayashi, Tomoe

× Kobayashi, Tomoe

WEKO 96057

en Kobayashi, Tomoe

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Fujii, Tsutomu

× Fujii, Tsutomu

WEKO 96058

en Fujii, Tsutomu

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Yamada, Suguru

× Yamada, Suguru

WEKO 96059

en Yamada, Suguru

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Yamaguchi, Junpei

× Yamaguchi, Junpei

WEKO 96060

en Yamaguchi, Junpei

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Wang, Tongtong

× Wang, Tongtong

WEKO 96061

en Wang, Tongtong

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Woods, Susan L.

× Woods, Susan L.

WEKO 96062

en Woods, Susan L.

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Worthley, Daniel

× Worthley, Daniel

WEKO 96063

en Worthley, Daniel

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Shimamura, Teppei

× Shimamura, Teppei

WEKO 96064

en Shimamura, Teppei

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Fujishiro, Mitsuhiro

× Fujishiro, Mitsuhiro

WEKO 96065

en Fujishiro, Mitsuhiro

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Hirooka, Yoshiki

× Hirooka, Yoshiki

WEKO 96066

en Hirooka, Yoshiki

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Enomoto, Atsushi

× Enomoto, Atsushi

WEKO 96067

en Enomoto, Atsushi

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Takahashi, Masahide

× Takahashi, Masahide

WEKO 96068

en Takahashi, Masahide

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
キーワード
主題Scheme Other
主題 Meflin
キーワード
主題Scheme Other
主題 cancer-associated fibroblasts
キーワード
主題Scheme Other
主題 pancreatic cancer
キーワード
主題Scheme Other
主題 pancreatic stellate cells
キーワード
主題Scheme Other
主題 tumor microenvironment
キーワード
主題Scheme Other
主題 lysyl oxidase
抄録
内容記述 Cancer-associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. Recent observations in genetically engineered mouse models and clinical studies have suggested that there may exist at least two functionally different populations of CAFs, that is, cancer-promoting CAFs (pCAF) and cancer-restraining CAFs (rCAF). Although various pCAF markers have been identified, the identity of rCAFs remains unknown because of the lack of rCAF-specific marker(s). In this study, we found that Meflin, a glycosylphosphatidylinositol-anchored protein that is a marker of mesenchymal stromal/stem cells and maintains their undifferentiated state, is expressed by pancreatic stellate cells that are a source of CAFs in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis of 71 human PDAC tissues revealed that the infiltration of Meflin-positive CAFs correlated with favorable patient outcome. Consistent herewith, Meflin deficiency led to significant tumor progression with poorly differentiated histology in a PDAC mouse model. Similarly, genetic ablation of Meflin-positive CAFs resulted in poor differentiation of tumors in a syngeneic transplantation model. Conversely, delivery of a Meflin-expressing lentivirus into the tumor stroma or overexpression of Meflin in CAFs suppressed the growth of xenograft tumors. Lineage tracing revealed that Meflin-positive cells gave rise to α-smooth muscle actin-positive CAFs that are positive or negative for Meflin, suggesting a mechanism for generating CAF heterogeneity. Meflin deficiency or low expression resulted in straightened stromal collagen fibers, which represent a signature for aggressive tumors, in mouse or human PDAC tissues, respectively. Together, the data suggest that Meflin is a marker of rCAFs that suppress PDAC progression.
言語 en
内容記述タイプ Abstract
内容記述
内容記述 ファイル公開:2020/10/01
言語 ja
内容記述タイプ Other
出版者
言語 en
出版者 American Association for Cancer Research
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1158/0008-5472.CAN-19-0454
ISSN(print)
収録物識別子タイプ PISSN
収録物識別子 0008-5472
書誌情報 en : Cancer Research

巻 79, 号 20, p. 5367-5381, 発行日 2019-10
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