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The function of cancer associated fibroblasts-derived exosomes on the energy metabolism of scirrhous type gastric cancer

Research Project

Project/Area Number 15K21646
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Experimental pathology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Naito Yutaka  国立研究開発法人国立がん研究センター, 研究所, 外来研究員 (70738210)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsExosome / microRNA / スキルス胃癌 / 癌関連線維芽細胞 / 代謝 / 癌微小環境 / メタボローム
Outline of Final Research Achievements

In the present study, we use co-culture system of fibroblasts with high-metastatic scirrhous gastric cancer (SGC) cells or low-metastatic SGC cells as a model to understand how to create favorable microenvironments for cancer metastasis. By comparing transcriptome profiles of fibroblasts co-cultured with high- or low-metastatic SGC cells, it revealed that glucose metabolism in fibroblasts was reprogrammed by co-culture with high-metastatic SGC cells. We also found that high-metastatic DGC-derived extracellular vesicles (EVs) dominantly induced inflammatory cytokines through TGF-β independent manner. Under co-culture condition also strongly induced the expressions of glycolysis-related genes and decreased the expression of oxidative phosphorylation-related genes in high-metastatic SGC cells. Thus, our finding suggests the cellular crosstalk between cancer cells and fibroblasts via EVs in SGC microenvironment.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] How cancer cells dictate their microenvironment: present roles of extracellular vesicles.2017

    • Author(s)
      Naito Y, Yoshioka Y, Yamamoto Y, Ochiya T.
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 74 Issue: 4 Pages: 697-713

    • DOI

      10.1007/s00018-016-2346-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transmission of HBV-DNA mediated by ceramide-triggered extracellular vesicles2016

    • Author(s)
      Takahiro Sanada, Yuichi Hirata, Yutaka Naito, Naoki Yamamoto, Yoshiaki Kikkawa, Yuji Ishida, Chihiro Yamasaki, Chise Tateno, Takahiro Ochiya, and *Michinori Kohara
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 3 Issue: 2 Pages: 272-283

    • DOI

      10.1016/j.jcmgh.2016.10.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Global, cancer-specific microRNA cluster hypomethylation was functionally associated with the development of non-B non-C hepatocellular carcinoma.2016

    • Author(s)
      Nojima M, Matsui T, Tamori A, Kubo S, Shirabe K, Kimura K, Shimada M, Utsunomiya T, Kondo Y, Iio E, Naito Y, Ochiya T, Tanaka Y.
    • Journal Title

      Molecular Cancer

      Volume: 15 Issue: 1 Pages: 31-31

    • DOI

      10.1186/s12943-016-0514-6

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fukutin, identified by the Escherichia coli ampicillin secretion trap (CAST) method, participates in tumor progression in gastric cancer.2016

    • Author(s)
      Oo HZ, Sentani K, Mukai S, Hattori T, Shinmei S, Goto K, Sakamoto N, Naito Y, Anami K, Trang PT, Yanagihara K, Oue N, Yasui W.
    • Journal Title

      Gastric Cancer

      Volume: 19 Issue: 2 Pages: 443-452

    • DOI

      10.1007/s10120-015-0511-2

    • NAID

      40020835493

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of miR-148a in Colorectal Neoplasia: Downregulation of miR-148a Contributes to the Carcinogenesis and Cell Invasion of Colorectal Cancer.2015

    • Author(s)
      Hibino Y, Sakamoto N, Naito Y, Goto K, Oo HZ, Sentani K, Hinoi T, Ohdan H, Oue N, Yasui W.
    • Journal Title

      Pathobiology

      Volume: 82 Issue: 5 Pages: 233-241

    • DOI

      10.1159/000438826

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors.2015

    • Author(s)
      Naito Y, Oue N, Pham TT, Yamamoto M, Fujihara M, Ishida T, Mukai S, Sentani K, Sakamoto N, Hida E, Sasaki H, Yasui W.
    • Journal Title

      Pathobiology

      Volume: 82 Issue: 2 Pages: 68-75

    • DOI

      10.1159/000398809

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] がんの新規診断・治療標的としてのエクソソームの応用と展開2015

    • Author(s)
      内藤 寛、吉岡 祐亮、落谷 孝広
    • Journal Title

      癌と化学療法

      Volume: 42 Pages: 647-655

    • Related Report
      2015 Research-status Report
  • [Journal Article] microRNAs and Hepatitis B.2015

    • Author(s)
      Naito Y, Tanaka Y, Ochiya T.
    • Journal Title

      microRNA: Medical Evidence, Advances in Experimental Medicine and Biology

      Volume: 888 Pages: 389-399

    • DOI

      10.1007/978-3-319-22671-2_19

    • ISBN
      9783319226705, 9783319226712
    • Related Report
      2015 Research-status Report
  • [Presentation] スキルス胃癌微小環境における癌関連線維芽細胞由来細胞外小胞の機能解析2016

    • Author(s)
      内藤 寛、八代 正和、清野 透、平川 弘聖、安井 弥、勝田 毅、落谷 孝広
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜 (神奈川県、横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] スキルス胃癌癌関連線維芽細胞に由来する分泌型microRNAの機能解析2016

    • Author(s)
      内藤 寛、吉岡 祐亮、山本 雄介、八代 正和、清野 透、平川 弘聖、安井 弥、落谷 孝広
    • Organizer
      第8回日本RNAi研究会・第3回日本細胞外小胞学会
    • Place of Presentation
      グランドプリンスホテル広島 (広島県、広島市)
    • Year and Date
      2016-08-31
    • Related Report
      2016 Annual Research Report
  • [Presentation] Functional roles of CaF-derived extracellular vesicles in scirrhous type gastric cancer2016

    • Author(s)
      Yutaka Naito, Takahiro Ochiya
    • Organizer
      Keystone symposia, Exosomes/Microvesicles: Novel Mechanisms of Cell-Cell Communication (E4)
    • Place of Presentation
      Keystone Resort, Keystone, Colorado, USA
    • Year and Date
      2016-06-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of extracellular vesicles in scirrhous type gastric cancer microenvironment.2016

    • Author(s)
      Yutaka Naito, Masakazu Yashiro, Kosei Hirakawa, Toru Kiyono, Wataru Yasui and Takahiro Ochiya.
    • Organizer
      International Society For Extracellular Vesicles (ISEV)2016. The Fifth International Meeting of ISEV.
    • Place of Presentation
      The Netherlands, Rotterdam
    • Year and Date
      2016-05-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional role of microRNA in scirrhous type gastric cancer microenvironment.2016

    • Author(s)
      Yutaka Naito
    • Organizer
      4th international Postgraduate Conference on Pharmaceutical Sciences 2016
    • Place of Presentation
      千葉、東京理科大学
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] スキルス胃癌微小環境における細胞外小胞の機能2015

    • Author(s)
      内藤 寛、八代 正和、平川 弘聖、安井 弥、落谷 孝広
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] スキルス胃癌微小環境における細胞外小胞の網羅的解析2015

    • Author(s)
      内藤 寛、八代 正和、平川 弘聖、安井 弥、落谷 孝広
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] スキルス胃癌微小環境における分泌型microRNAの機能解析2015

    • Author(s)
      内藤 寛、八代 正和、平川 弘聖、安井 弥、落谷 孝広
    • Organizer
      第7回日本RNAi研究会・第2回日本細胞外小胞学
    • Place of Presentation
      広島
    • Year and Date
      2015-08-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Functional analysis of extracellular vesicles as a novel regulatory agent of scirrhous type gastric cancer microenvironment.2015

    • Author(s)
      Yutaka Naito, Masakazu Yashiro, Kosei Hirakawa, Wataru Yasui, Takahiro Ochiya.
    • Organizer
      International Society For Extracellular Vesicles (ISEV) 2015
    • Place of Presentation
      America, Washington, D.C.
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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