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Molecular analysis on neoplastic survival of mast cells in a poor microenvironment

Research Project

Project/Area Number 24380168
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Clinical veterinary science
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

TANAKA Akane  東京農工大学, (連合)農学研究科(研究院), 教授 (80418673)

Co-Investigator(Kenkyū-buntansha) KISHIMOTO Miori  東京農工大学, 大学院農学研究院, 講師 (50588960)
MATSUDA Akira  東京農工大学, 大学院農学研究院, 助教 (90613969)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Keywords獣医学 / 腫瘍 / ストレス応答 / 低酸素
Outline of Final Research Achievements

In the current study, I explored the molecular mechanisms which underpins neoplastic proliferation and survival of mast cells in a poor micro environment. Particularly, stress response and intracellular metabolism of malignant mast cells were investigated. Cytokines that induce neovasclarization were up-regulated when mouse bone marrow-derived cultured mast cells were incubated in hypoxic condition. Relative hypoxia, but not hyperoxia, induced degranulation of mast cells in antigen and IgE independent manner. Not only production of angiogenic factors but also glycolysis were promoted in mast cells derived from canine mast cell tumor. In addition, acceleration of endoplasmic reticulum responses was identified in malignant but not normal mast cells. These results suggest that aggravation of above mentioned responses to hypoxia and lack of nutrition might involve in rapid growth of neoplastic mast cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (23 results)

All 2015 2014 2013 2012 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 1 results) Book (2 results) Remarks (3 results)

  • [Journal Article] A point mutation in the extracellular domain of KIT promotes tumorigenesis of mast cells via ligand-independent auto-dimerization2015

    • Author(s)
      Amagai Y, Matsuda A, Jung K, Oida K, Jang H, Ishizaka S, Matsuda H, Tanaka A
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 9775-9775

    • DOI

      10.1038/srep09775

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer.2015

    • Author(s)
      Jensen-Jarolim E, Fazekas J, Singer J, Hofstetter G, Oida K, Matsuda H, Tanaka A.
    • Journal Title

      Cancer Immunology and Immunotherapy

      Volume: 64 Issue: 5 Pages: 531-537

    • DOI

      10.1007/s00262-015-1684-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cervical branch of the facial nerve approach for retrograde parotidectomy compared with anterograde parotidectomy.2014

    • Author(s)
      Furusaka T, Tanaka A, Matsuda H, Hasegawa H, Asakawa T, Shigihara S.
    • Journal Title

      Acta Otolaryngology

      Volume: 134 Issue: 11 Pages: 1192-1197

    • DOI

      10.3109/00016489.2014.900701

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear factor-kappaB plays a critical role in both intrinsic and acquired resistance against endocrine therapy in human breast cancer cells.2014

    • Author(s)
      Oida K, Matsuda A, Jung K, Xia Y, Jang H, Amagai Y, Ahn G, Nishikawa S, Ishizaka S, Jensen-Jarolim E, Matsuda H, Tanaka A.
    • Journal Title

      Scientific Reports

      Volume: 4 Issue: 1 Pages: 4057-4057

    • DOI

      10.1038/srep04057

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A molecular targeting against nuclear factor-kappaB, as a chemotherapeutic approach for human malignant mesothelioma.2014

    • Author(s)
      Nishikawa S, Tanaka A, Matsuda A, Oida K, Jang H, Jung K, Amagai Y, Ahn G, Okamoto N, Ishizaka S, Matsuda H.
    • Journal Title

      Cancer Medicine

      Volume: 3416-25. Issue: 2 Pages: 416-425

    • DOI

      10.1002/cam4.202

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of stem cell factor in canine mast cell tumors.2014

    • Author(s)
      Amagai Y, Tanaka A, Jung K, Matsuda A, Oida K, Nishikawa S, Jang H, Ishizaka S, Matsuda H.
    • Journal Title

      Research in Veterinary Science

      Volume: 96 Issue: 1 Pages: 124-126

    • DOI

      10.1016/j.rvsc.2013.10.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem cell factor contributes to tumorigenesis of mast cells via an autocrine/paracrine mechanism.2013

    • Author(s)
      Amagai Y, Tanaka A, Matsuda A, Jung K, Ohmori K, Matsuda H.
    • Journal Title

      J. Leukoc. Biol.

      Volume: 93(2) Issue: 2 Pages: 245-250

    • DOI

      10.1189/jlb.0512245

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of internal tandem duplications in the c-kit of dogs with multiple mast cell tumors2013

    • Author(s)
      Amagai Y, Akane T, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Matsuda H
    • Journal Title

      J. Small Anim. Prac

      Volume: (In press) Issue: 7 Pages: 377-380

    • DOI

      10.1111/jsap.12069

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Phosphoinositide 3-Kinase Pathway Is Crucial for the Growth of Canine Mast Cell Tumors.2013

    • Author(s)
      Amagai Y, Tanaka A, Matsuda A, Oida K, Jung K, Matsuda H.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: (In press)

    • NAID

      40019727423

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Expression of the Antiapoptotic Protein MCL1 in Canine Mast Cell Tumors.2013

    • Author(s)
      Amagai Y, Tanaka A, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Ishizaka S, Matsuda H.
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: (In press)

    • NAID

      130003362156

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of nuclear factor-κB in both intrinsic and acquired resistance against endocrine therapy in breast cancer2014

    • Author(s)
      Tanaka A, Oida K, Amagai Y, Matsuda H
    • Organizer
      19th World Congress on Advances in Oncology & 17th International Symposium on Molecular Medicine
    • Place of Presentation
      ギリシャ、アテネ
    • Year and Date
      2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] イヌ肥満細胞腫におけるc-kit mRNA全長の塩基配列解析2012

    • Author(s)
      北村亮、田中あかね, 他
    • Organizer
      日本獣医学会
    • Place of Presentation
      岩手県盛岡市・岩手大学
    • Year and Date
      2012-09-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] イヌ肥満細胞腫における幹細胞因子自己産生メカニズム2012

    • Author(s)
      雨貝陽介、田中あかね, 他
    • Organizer
      日本獣医学会
    • Place of Presentation
      岩手県盛岡市・岩手大学
    • Year and Date
      2012-09-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] NF-kappaB, a new target molecule in treatment of mesothelioma 18th World Congress on Advances in Oncology

    • Author(s)
      Oida K, Nishikawa S, Tanaka a, Matsuda H.
    • Organizer
      18th World Congress on Advances in Oncology
    • Place of Presentation
      ギリシャ、クレタ
    • Related Report
      2013 Annual Research Report
  • [Presentation] KIT細胞膜外ドメインの点変異による肥満細胞の腫瘍化

    • Author(s)
      雨貝陽介、田中あかね、松田彬、松田浩珍
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜県岐阜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] KIT細胞外ドメインの点変位による肥満細胞の腫瘍化

    • Author(s)
      雨貝陽介、松田彬、田中あかね、松田浩珍
    • Organizer
      CBSM2013
    • Place of Presentation
      山梨県石和市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Splicing regulation of glucocorticoid receptor isoforms in lymphocytes with glucocoriticoid resistance

    • Author(s)
      Tanaka A, Matsuda A, Amagai Y, Matsuda H.
    • Organizer
      欧州アレルギー臨床免疫学会
    • Place of Presentation
      イタリア、ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] House dust mite allergens induce IgE-independent activation of canine mast cells NI-1

    • Author(s)
      Oida K, Tanaka A, Matsuda H, Jensen-Jarolim E.
    • Organizer
      Annual Meeting "Veterinaerimmunologischer Arbeitskreis" of the German Society for Immunology
    • Place of Presentation
      ドイツ、ミュンヘン
    • Related Report
      2013 Annual Research Report
  • [Book] 肥満細胞腫における分子標的治療法の最近の知見(J-vet)2012

    • Author(s)
      田中あかね、雨貝陽介、松田浩珍
    • Publisher
      株式会社インターズー
    • Related Report
      2012 Annual Research Report
  • [Book] 肥満細胞の腫瘍化メカニズム(J-vet)2012

    • Author(s)
      田中あかね、松田彬、雨貝陽介、松田浩珍
    • Publisher
      株式会社インターズー
    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究室HP

    • URL

      http://www.tuat.ac.jp/~mol_path/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.tuat.ac.jp/~mol_path/

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://www.tuat.ac.jp/~mol_path

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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