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Mechanistic analysis of cooperative invasion between cancer cells and stromal fibroblasts

Research Project

Project/Area Number 16K14616
Research Category

Grant-in-Aid for Challenging Exploratory Research

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

Principal Investigator

Sakai Ryuichi  北里大学, 医学部, 教授 (40215603)

Co-Investigator(Kenkyū-buntansha) 山口 英樹  公益財団法人佐々木研究所, 附属研究所, 部長(移行) (10345035)
Research Collaborator Kurosawa Gene  
Shirakihara Takuya  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsスキルス胃がん / 間質線維芽細胞 / ファージ抗体 / 癌間質相互作用 / 癌微小環境 / 細胞間接着 / がん間質相互作用 / CAF / Dasatinib / 微小環境 / 癌 / 細胞・組織
Outline of Final Research Achievements

It is recently highlighted that the interaction between cancer cells and surrounding stromal fibroblasts is deeply involved in the regulation of growth, metastasis and invasion of cancers. In this study, we established a new approach to reveal molecules regulating this interaction by using three dimension co-culture method along with the screening of the phage display antibody library. Several candidates of the phage antibody clones are picked up using this new technology.

Academic Significance and Societal Importance of the Research Achievements

近年種々の腫瘍で腫瘍細胞と間質細胞の相互作用が腫瘍の悪性化の制御因子として着目されているが、細胞間の相互作用は通常の分子生物学的、細胞生物学的手法のアプローチに限界があるため、この相互作用の鍵となる分子の探索は進んでいない。本研究によりマトリゲル上の3D共培養を用いた浸潤能の定量とファージディスプレイ抗体ライブラリーを用いた全く新しいスクリーニング手法を確立することができたことは、多くの腫瘍の腫瘍間質相互作用の解析に応用可能であると考える。また本研究で候補として挙がってきた分子は、全く新しいスキルス胃癌の治療法開発の糸口となりうると考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The p53 activator overcomes resistance to ALK inhibitors by regulating p53-target selectivity in ALK-driven neuroblastomas2018

    • Author(s)
      Miyazaki Makoto、Otomo Ryo、Matsushima-Hibiya Yuko、Suzuki Hidenobu、Nakajima Ayana、Abe Naomi、Tomiyama Arata、Ichimura Koichi、Matsuda Koichi、Watanabe Toshiki、Ochiya Takahiro、Nakagama Hitoshi、Sakai Ryuichi、Enari Masato
    • Journal Title

      Cell Death Discovery

      Volume: 4 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41420-018-0059-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft2018

    • Author(s)
      Yamamoto Yutaro、Tomiyama Arata、Sasaki Nobuyoshi、Yamaguchi Hideki、Shirakihara Takuya、Nakashima Katsuhiko、Kumagai Kosuke、Takeuchi Satoru、Toyooka Terushige、Otani Naoki、Wada Kojiro、Narita Yoshitaka、Ichimura Koichi、Sakai Ryuichi、Namba Hiroki、Mori Kentaro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 1 Pages: 1292-1299

    • DOI

      10.1016/j.bbrc.2017.11.113

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant alternative splicing of RHOA is associated with loss of its expression and activity in diffuse-type gastric carcinoma cells2018

    • Author(s)
      Miyamoto Shingo、Nagamura Yuko、Nakabo Ayaka、Okabe Akira、Yanagihara Kazuyoshi、Fukami Kiyoko、Sakai Ryuichi、Yamaguchi Hideki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 2 Pages: 1942-1947

    • DOI

      10.1016/j.bbrc.2017.12.067

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel small molecule inhibiting CDCP1-PKCδ pathway reduces tumor metastasis and proliferation.2017

    • Author(s)
      Nakashima K, Uekita T, Yano S, Kikuchi JI, Nakanishi R, Sakamoto N, Fukumoto K, Nomoto A, Kawamoto K, Shibahara T, Yamaguchi H, Sakai R.
    • Journal Title

      Cancer Sci.

      Volume: 印刷中 Issue: 5 Pages: 1049-1057

    • DOI

      10.1111/cas.13218

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Actinin-1 and actinin-4 play essential but distinct roles in invadopodia formation by carcinoma cells2017

    • Author(s)
      Yamaguchi Hideki、Ito Yuumi、Miura Nami、Nagamura Yuko、Nakabo Ayaka、Fukami Kiyoko、Honda Kazufumi、Sakai Ryuichi
    • Journal Title

      European Journal of Cell Biology

      Volume: 96 Issue: 7 Pages: 685-694

    • DOI

      10.1016/j.ejcb.2017.07.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Identification and functional analysis of FGFR2 binding proteins in schirrous gastric cancer2019

    • Author(s)
      Shirakihara T, Sakai R
    • Organizer
      11th AACR-JCA Joint Conference : Breakthrough in Cancer Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification and functional analysis of FGFR2 binding proteins in diffuse-type gastric carcinoma2019

    • Author(s)
      Shirakihara T, Sakai R
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] スキルス胃がんの進展に寄与するFGF受容体結合タンパク質の探索と機能解析2018

    • Author(s)
      白木原琢哉、堺隆一
    • Organizer
      第27回日本がん転移学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スキルス胃がんと間質線維芽細胞の直接的な相互作用に関わる分子機構の解明2018

    • Author(s)
      宮本真吾、堺隆一、山口英樹
    • Organizer
      第27回日本がん転移学会学術集会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スキルス胃がんの進展に関わるFGFR2結合タンパク質の探索と機能解析2018

    • Author(s)
      白木原琢哉、堺隆一
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] びまん性胃がんにおけるRhoAのスプライシング異常とそれに伴う発現及び活性の低下2018

    • Author(s)
      宮本真吾、中坊彩花、深見希代子、柳原五吉、堺隆一、山口英樹
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] スキルス胃がんの悪性化に関わる受容体チロシンキナーゼ標的タンパク質の探索と機能解析2017

    • Author(s)
      白木原琢哉、堺隆一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] スキルス胃癌細胞におけるSHP2の機能解析2017

    • Author(s)
      山口英樹、富山新太、堺隆一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] スキルス胃癌細胞の増殖及び浸潤転移におけるSHP2の機能解析2017

    • Author(s)
      山口英樹、堺隆一
    • Organizer
      第26回日本がん転移学会学術集会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Interaction between carcinoma cells and stromal fibroblasts during invasion and metastasis of scirrhous gastric carcinoma2016

    • Author(s)
      山口英樹、柳原五吉、八代正和、堺隆一
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] スキルス胃がんにおける新規チロシンリン酸化タンパク質PLEKHA5の機能解析2016

    • Author(s)
      山口英樹、白木原琢哉、堺隆一
    • Organizer
      第75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 Research-status Report
  • [Presentation] スキルス胃がんにおける活性化受容体型チロシンキナーゼ結合蛋白質の同定と機能解析2016

    • Author(s)
      白木原琢哉、山口英樹、堺隆一
    • Organizer
      第75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 Research-status Report
  • [Presentation] スキルス胃がん細胞におけるPLEKHA5の機能解析2016

    • Author(s)
      山口英樹、白木原琢哉、堺隆一
    • Organizer
      第25回日本がん転移学会学術集会・総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2016-07-21
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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