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Establishment of new target therapy depending on the origin of lung cancer stem cell

Research Project

Project/Area Number 26461170
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKansai Medical University

Principal Investigator

KUMANO Keiki  関西医科大学, 医学部, 准教授 (90396721)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺がん / 幹細胞 / 系譜追跡 / Bmi1
Outline of Final Research Achievements

Alveolar stem cells were tracked by lineage tacing system. Among stem cell markers, Bmi1 expressed in the some portion of alveolar type 2(AT2) cells (SPC(+) cells). After Radiation injury, both AT2 and AT1 cells were regenerated from Bmi1(+) cells.
Mutant form of Kras (Kras G12D) caused the clonal lung cancer development from one Bmi1(+) cells. On the other hand, all mice died after mutnat Kras was expressed in the SPC(+) alveolar type 2 cells within 8weeks. In this time point, the clonal expansion of SPC(+) cells were observed but no obvious lung cancer developed. This indicate that mice were dead due to the suffocation probably by the oversecretion of surfactant proteins. These results indicate lung cancer might be originated from the Bmi1(+) cells which are some part of AT2 cells.

Report

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

    (9 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion.2017

    • Author(s)
      Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon and Ueno H.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 41838-41847

    • DOI

      10.1038/srep41838

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer2016

    • Author(s)
      T Tanaka, N Atsumi, N Nakamura, H Yanai, Y Komai, T Omachi, K Tanaka, K Ishigaki, K Saiga, H Ohsugi, Y Tokuyama, Y Imahashi, H Hisha, N Yoshida, K Kumano, K Okazaki, and Ueno H
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 39386-39391

    • DOI

      10.1038/srep39386

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maintenance of sweat glands by stem cells located in the acral epithelium.2015

    • Author(s)
      1.Ohe S, Tanaka T, Yanai H, Komai Y, Omachi T, Kanno S, Tanaka K, Ishigaki K, Saiga K, Nakamura N, Ohsugi H, Tokuyama Y, Atsumi N, Hisha H, Yoshida N, Kumano K, Yamazaki F, Okamoto H, Ueno H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466 Issue: 3 Pages: 333-338

    • DOI

      10.1016/j.bbrc.2015.09.022

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeted gene correction of RUNX1 in induced pluripotent stem cells derived from familial platelet disorder with propensity to myeloid malignancy restores normal megakaryopoiesis.2015

    • Author(s)
      2.Iizuka H, Kagoya Y, Kataoka K, Yoshimi A, Miyauchi M, Taoka K, Kumano K, Yamamoto T, Hotta A, Arai S, Kurokawa M.
    • Journal Title

      Exp Hematol.

      Volume: 43 Issue: 10 Pages: 849-857

    • DOI

      10.1016/j.exphem.2015.05.004

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intracellular signals of lung cancer cells as possible therapeutic targets.2015

    • Author(s)
      Tanaka K, Kumano K, Ueno H
    • Journal Title

      Cancer Science

      Volume: 未定 Issue: 5 Pages: 489-496

    • DOI

      10.1111/cas.12643

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bmi1 expression in long-term germ stem cells.2014

    • Author(s)
      Komai Y, Tanaka T, Tokuyama Y, Yanai H, Ohe S, Omachi T, Atsumi N, Yoshida N, Kumano K, Hisha H, Matsuda T, Ueno H.
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 6175-6186

    • DOI

      10.1038/srep06175

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples2014

    • Author(s)
      Hosoi M, Kumano K, Taoka K, Arai S, Kataoka K, Ueda K, Kamikubo Y, Takayama N, Otsu M, Eto K, Nakauchi H, Kurokawa M
    • Journal Title

      Exp Hematol

      Volume: (in press) Issue: 9 Pages: 816-25

    • DOI

      10.1016/j.exphem.2014.03.010

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The IL-2/CD25 Axis Maintains Distinct Subsets of Chronic M yeloid Leukemia-initiating Cells.2014

    • Author(s)
      Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T.
    • Journal Title

      Blood

      Volume: 123 Issue: 16 Pages: 2540-2549

    • DOI

      10.1182/blood-2013-07-517847

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity.2014

    • Author(s)
      Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
    • Journal Title

      J Clin Invest.

      Volume: 124 Issue: 2 Pages: 528-542

    • DOI

      10.1172/jci68101

    • Related Report
      2014 Research-status Report
    • Peer Reviewed

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

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