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Analysis of Cancer cell death induced by "Death-touch"

Research Project

Project/Area Number 26640068
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionAkita University

Principal Investigator

Tanaka Masamitsu  秋田大学, 医学(系)研究科(研究院), 教授 (20291396)

Co-Investigator(Renkei-kenkyūsha) KURIYAMA SEI  秋田大学, 医学部, 准教授 (30398226)
ITOH GO  秋田大学, 医学部, 助教 (60607563)
Project Period (FY) 2014-04-01 – 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsスキルス胃癌 / 癌関連線維芽細胞 / CAF / アポトーシス / 細胞外小胞 / 播種 / 細胞間接触 / デスタッチ / 癌間質細胞
Outline of Final Research Achievements

We found that CAFs induce apoptosis in gastric cancer cells, which switches the invasion mode of tumors. Death receptor 4 and activation of caspase-8 in cancer cells mediated cancer cell apoptosis induced by CAFs, which was dependent on contact between cancer cells and CAFs. Apoptotic cancer cells in turn released apoptotic vesicles and stimulated invasion of CAFs. Accordingly, cancer cells followed the migrating CAFs. Treatment with a caspase inhibitor, ZVAD, or forced expression of a death domain (DD) fragment in cancer cells prevented cancer cell apoptosis induced by CAFs and increased expansive invasion by cancer cells in extracellular gel invasion assays, while the rate of cancer cell invasion led by CAFs was decreased. Because CAF-led invasion is characterized by the movement of individual cancer cells away from the tumor, adequate cancer cell apoptosis may promote cancer dissemination.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (29 results)

All 2017 2016 2015 Other

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 6 results,  Acknowledgement Compliant: 10 results) Presentation (14 results) Remarks (2 results)

  • [Journal Article] Cancer-associated fibroblasts induce cancer cell apoptosis that regulates invasion mode of tumors.2017

    • Author(s)
      Itoh G., Chida S., Yanagihara K., Yashiro M., Aiba N., Tanaka M.
    • Journal Title

      Oncogene

      Volume: 印刷中 Issue: 31 Pages: 4434-4444

    • DOI

      10.1038/onc.2017.49

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mesothelial cells create a novel tissue niche that facilitates gastric cancer invasion2017

    • Author(s)
      Tanaka M., Kuriyama S., Itoh G., Maeda D., Goto A., Tamiya Y., Yanagihara K., Yashiro M., Aiba N.
    • Journal Title

      Cancer Research

      Volume: 77 Issue: 3 Pages: 684-695

    • DOI

      10.1158/0008-5472.can-16-0964

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spatiotemporal expression of UPK3B and its promoter activity during embryogenesis and spermatogenesis2017

    • Author(s)
      Kuriyama S, Tamiya Y, Tanaka M
    • Journal Title

      Histochem Cell Biol

      Volume: 147 Issue: 1 Pages: 17-26

    • DOI

      10.1007/s00418-016-1486-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube2016

    • Author(s)
      Kito M, Maeda D, Kudo-Asabe Y, Sato N, Shih IeM, Wang TL, Tanaka M, Terada Y, Goto A
    • Journal Title

      PLoS One

      Volume: 11 Issue: 6 Pages: e0156069-e0156069

    • DOI

      10.1371/journal.pone.0156069

    • NAID

      120007089065

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SKAP2 promotes podosome formation to facilitate tumor-associated macrophage infiltration and metastatic progression.2016

    • Author(s)
      Tanaka M, Shimamura S, Kuriyama S, Maeda D, Goto A and Aiba N.
    • Journal Title

      Cancedr Research

      Volume: 176 Issue: 2 Pages: 358-369

    • DOI

      10.1158/0008-5472.can-15-1879

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of anti-cancer chemical compounds using Xenopus embryos.2016

    • Author(s)
      Tanaka M, Kuriyama S, Itoh G, Kohyama A, Iwabuchi Y, Shibata H, Yashiro M, Aiba N.
    • Journal Title

      Cancer Science

      Volume: -

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A curcumin analog, GO-Y078, effectively inhibits angiogenesis through actin disorganization.2016

    • Author(s)
      Sugiyama S., Yoshino Y., Kuriyama S., Inoue M, Komine K, Otsuka K, Kohyama A, Yamakoshi H, Ishioka C, Tanaka M, Iwabuchi Y, Shibata H.
    • Journal Title

      Anti-Cancer Agents in Medicinal Chemistry

      Volume: 16 Pages: 633-647

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 3D Gel Invasion Assay of Gastric Cancer cells with Fibroblasts.2016

    • Author(s)
      Tanaka M
    • Journal Title

      Bio Protoc

      Volume: 6

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] LPP inhibits collective cell migration during lung cancer dissemination2015

    • Author(s)
      Kuriyama S., Yoshida M., Yano S., Aiba N., Kohno T., Minamiya Y., Goto A., Tanaka M.
    • Journal Title

      Oncogene

      Volume: - Issue: 8 Pages: 952-964

    • DOI

      10.1038/onc.2015.155

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Agr2 mediates paracrine effects on stromal fibroblasts that promote invasion by gastric signet-ring carcinoma cells2015

    • Author(s)
      Tsuji T., Satoyoshi R., Aiba N., Kubo T., Yanagihara K., Maeda D., Goto A., Ishikawa K., Yashiro M., Tanaka M
    • Journal Title

      Cancer Research

      Volume: 75 Issue: 2 Pages: 356-366

    • DOI

      10.1158/0008-5472.can-14-1693

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Tks5 activation in mesothelial cells creates invasion front of peritoneal carcinomatosis2015

    • Author(s)
      Satoyoshi R., Aiba N., Yanagihara K., Yashiro M., Tanaka M
    • Journal Title

      Oncogene

      Volume: - Issue: 24 Pages: 3176-3187

    • DOI

      10.1038/onc.2014.246

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Asporin activates coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts.2015

    • Author(s)
      Satoyoshi R, Kuriyama S, Aiba N, Yashiro M, Tanaka M.
    • Journal Title

      Oncogene.

      Volume: 34 Issue: 5 Pages: 650-660

    • DOI

      10.1038/onc.2013.584

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] LPP inhibits collective cell migration during lung cancer dissemination2015

    • Author(s)
      Sei Kuriyama, Makoto Yoshida, Seiji Yano, Namiko Aiba,Takashi Kohno, Yoshihiro Minamiya, Akiteru Goto and Masamitsu Tanaka
    • Journal Title

      Oncogene

      Volume: -

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] CAF(癌関連線維芽細胞)は癌細胞の細胞死を誘導する事で癌浸潤モードを制御する2016

    • Author(s)
      伊藤 剛、田中正光
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mesothelial cells create a novel niche that facilitates gastric cancer invasion2016

    • Author(s)
      田中正光
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] PLEKHN1 is rerquired for Bax oligomerization in cancer cell line2016

    • Author(s)
      栗山 正、田中正光
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mesothelial cells create a novel niche that attracts cancer invasion and peritonitis2016

    • Author(s)
      田中正光
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台国際センター会議場
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] アフリカツメガエル初期胚を利用した癌細胞の集団的浸潤を抑制する化合物のスクリーニング2015

    • Author(s)
      田中正光
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Paracrine effcet of Agr2 on stromal fibroblasts promotes tumor invasion of gastric signet-ring cell carcinoma2015

    • Author(s)
      田中正光
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-11-25 – 2015-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] SKAP2 is required for macrophages in cancer progression.2015

    • Author(s)
      田中正光
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] LPP inhibits collective cell migration during lung cancer dissemination.2015

    • Author(s)
      栗山 正、田中正光
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Removal system of gastric cancer invasion by stromal cells.2015

    • Author(s)
      伊藤 剛、田中正光
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] The role of fatty acid binding protein 4 in prostate cancer progression.2015

    • Author(s)
      黄 明国、田中正光
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Paracrine effcet of Agr2 on stromal fibroblasts promotes tumor invasion of gastric signet-ring cell carcinoma2015

    • Author(s)
      田中正光
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-09-25 – 2015-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] LPP inhibits collective cell migration during lung cancer metastasis2015

    • Author(s)
      栗山 正
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-09-25 – 2015-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] SKAP2 suppersses breast cancer progression2015

    • Author(s)
      島村真太郎
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-09-25 – 2015-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Coordinated invasion of macrophages and cancer cells.2015

    • Author(s)
      田中正光
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report
  • [Remarks] 秋田大学大学院医学系研究科 分子生化学講座

    • URL

      http://www.med.akita-u.ac.jp/department/gs/kenkyu-org/kouza.php?koza=seika2

    • Related Report
      2016 Annual Research Report
  • [Remarks] 秋田大学大学院医学系研究科分子生化学講座

    • URL

      http://www.med.akita-u.ac.jp/department/gs/kenkyu-org/kouza.php?koza=seika2

    • Related Report
      2015 Research-status Report 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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