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The role of TGF-b signaling in blood and lymph angiogenesis

Research Project

Project/Area Number 23689023
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

ITOH Fumiko  東京薬科大学, 生命科学部, 准教授 (70502582)

Project Period (FY) 2011-11-18 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsTGF-β / 血管新生 / リンパ管新生 / 腫瘍 / 転移 / 遺伝子改変マウス / がん転移 / タモキシフェン / リンパ管 / 腫瘍血管新生 / 腫瘍リンパ管新生 / 低酸素 / E2-2 / FAM96B
Research Abstract

It is not clear how TGF-b signaling affects vascular formation in postnatal mice. To address this issue, TGF-b type II receptor conditional knockout (CKO) mice; TbRIIF/F, were crossed with Pdgfb-icreER and Prox1-CreERT2 mice in which Cre recombinase is induced in blood (BECs) and lymphatic vascular endothelial cells (LECs) by tamoxifen (Tx), respectively.
When LLC cells were subcutaneously injected into TbRIIF/F; Pdgfb-icreER (TbRIIBEC-CKO), TbRII;Prox1-CreERT2 (bRIILEC-CKO) mice , both tumor and lymphangiogenesis were enhanced in CKO mice. Moreover, lung metastasis was decreased when B16 melanoma cells were injected into foot pad in both CKO mice. Blood vessels in the tumor but not in the normal tissue of TbRIIBEC-CKO mice were very leaky, indicating the poor blood circulation in tumors. Furthermore, deletion of TGF-b signaling in LEC resulted in the reduced drainage and edema. These results indicated that TGF-b signaling inhibits tumor angiogenesis and lymphangiogenesis in adults.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (22 results) (of which Invited: 2 results) Book (8 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] C18ORF1: A Novel Negative Regulator of TGF-β Signaling.2014

    • Author(s)
      2. Nakano N, Maeyama K, Ikeno S, Itoh F, Togawa Y, Katsu Y, Thanh Thao, VN, Watanabe Y, Kato M & Itoh, S.
    • Journal Title

      J. Biol. Chem.,

      Volume: 289 Issue: 18 Pages: 12680-12680

    • DOI

      10.1074/jbc.m114.558981

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C18ORF1: A Novel Negative Regulator of TGF-βSignaling2012

    • Author(s)
      Nakano, N., Maeyama, K., Ikeno, S., Itoh, F., Togawa, Y., Katsu, Y., Thanh Thao, V.N., Watanabe, Y., Kato, M., and Itoh, S
    • Journal Title

      J. Biol. Chem

      Volume: 289 Pages: 12680-12692

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] (^#equally contributed) Smad2/ Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions2012

    • Author(s)
      Itoh F, Itoh S, Adachi T, Ichikawa K, Matsumura Y, Takagi T, Festing T, Watababe T, Weinstein M, Karlsson S &Kato M
    • Journal Title

      Blood

      Volume: 119 Pages: 5320-5328

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Implication of TGF-βas a survival for during tumor development2012

    • Author(s)
      Itoh S & Itoh F
    • Journal Title

      J. Biochem

      Volume: 151 Pages: 559-562

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions.2012

    • Author(s)
      Itoh F. et al.
    • Journal Title

      Blood

      Volume: 119 Issue: 22 Pages: 5320-5328

    • DOI

      10.1182/blood-2011-12-395772

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mplication of TGF-β as a survival factor during tumour development.2012

    • Author(s)
      Itoh S.
    • Journal Title

      J. Biochem.

      Volume: 151 Issue: 6 Pages: 559-562

    • DOI

      10.1093/jb/mvs042

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous bioactive peptides as biomarkers for atherosclerotic coronary heart disease.2012

    • Author(s)
      Watanabe T, et al.
    • Journal Title

      Sensors (Basel)

      Volume: 12 Issue: 4 Pages: 4974-4985

    • DOI

      10.3390/s120404974

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenic involvement of heregulin-β1 in anti-atherogenesis.2012

    • Author(s)
      Watanabe T, et al.
    • Journal Title

      Regulatory Peptides

      Volume: 175 Issue: 1-3 Pages: 11-14

    • DOI

      10.1016/j.regpep.2012.01.004

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory machinery for the TGF-βfamily signaling pathway2011

    • Author(s)
      Itoh F & Itoh S
    • Journal Title

      Growth Factors

      Volume: 29(5) Pages: 163-73

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] (^# equally contributed) Interference of E2-2-mediated effect in endothelial cells by FAM96B through its limited expression of E2-22011

    • Author(s)
      Yang W, Itoh F, Ohya H, Kishimoto F, Tanaka A, Nakano N, Itoh S & Kato M.
    • Journal Title

      Cancer Sci

      Volume: 102 Pages: 1808-1814

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interference of E2-2-mediated effect in endothelial cells by FAM96B through its limited expression of E2-22011

    • Author(s)
      Yang W., Itoh F., Ohya H., Kishimoto F., Tanaka A., Nakano N., Itoh S., Kato M
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 10 Pages: 1808-1814

    • DOI

      10.1111/j.1349-7006.2011.02022.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory machinery for the TGF-β family signaling pathway2011

    • Author(s)
      Itoh F, 他
    • Journal Title

      Growth Factors

      Volume: 29 Issue: 5 Pages: 163-173

    • DOI

      10.3109/08977194.2011.614236

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The roles of salusins in atherosclerosis and related cardiovascular diseases2011

    • Author(s)
      Watanabe T, 他
    • Journal Title

      J.Am.Soc.Hypertens.

      Volume: 5 Issue: 5 Pages: 359-365

    • DOI

      10.1016/j.jash.2011.06.003

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] TGF-βsignaling regulates lymphangiogenesis in vivo2014

    • Author(s)
      Itoh, F
    • Organizer
      Gordon Research Conferences. Molecular Mechanisms in Lymphatic Function & Disease
    • Place of Presentation
      Lucca (Barga), Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of TGF-βsignaling in Tumor blood- and lymph angiogenesis2013

    • Author(s)
      Itoh, F., Takagi, T., Ichikawa, K., Fruttiger, M., Oliver, G., Itoh S., and Watanabe, T
    • Organizer
      The 3^<rd> International Symposium by JSPS Core-to-Core Program"Cooperative International Frame work in TGF-βFamily Signaling"
    • Place of Presentation
      Matsuyama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF-βsignaling controls tumor blood- and lymph- angiogenesis. FASEB Summer Research conference2013

    • Author(s)
      Itoh, F., Takagi, T., Ichikawa, K., Fruttiger, M, Oliver, G., Watanabe, T., and Itoh, S
    • Organizer
      TGF-βsuperfamily : Signaling in Development and Disease
    • Place of Presentation
      Steamboat springs, Colorado, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of TGF-βsignaling in blood- and lymph- angiogenesis2013

    • Author(s)
      Itoh, F
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF-β signaling regulates lymphang iogenesis in mice development2012

    • Author(s)
      伊東史子
    • Organizer
      第1回先端研究拠点事業TGF-β国際シンポジウム
    • Place of Presentation
      東京大学小柴ホール
    • Year and Date
      2012-01-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions2012

    • Author(s)
      Itoh, F
    • Organizer
      17th International Vascular Biology Meeting
    • Place of Presentation
      Wiesbaden, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Dicer-dependent miRNA pathway is important for vascular development2012

    • Author(s)
      Itoh, F., Hazome, S., Fruttiger, M., Itoh, S., and Watanabe, T
    • Organizer
      10th Korea-Japan Joint Symposium on Vasuclar Biology
    • Place of Presentation
      Tokushima, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions.2012

    • Author(s)
      F.Itoh
    • Organizer
      17th International Vascular Biology Meeting
    • Place of Presentation
      Wiesbaden, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] TGF-β signaling regulates lymphangiogenesis in mice development.2012

    • Author(s)
      F.Itoh
    • Organizer
      17th International Vascular Biology Meeting
    • Place of Presentation
      Wiesbaden, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] Lack of TGF-β signaling promotes lymphangiogenesis in vivo.2012

    • Author(s)
      Ichikawa K.
    • Organizer
      2nd International Symposium by JSPS Core-to-Core Program "TGF-β Family: Signal Network and Tumor Microenvironment,
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Endothelial TGF-β signaling inhibits tumor angiogenesis.2012

    • Author(s)
      Takagi T.
    • Organizer
      2nd International Symposium by JSPS Core-to-Core Program "TGF-β Family: Signal Network and Tumor Microenvironment,
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dicer-dependent miRNA pathway is important for vascular development.2012

    • Author(s)
      Itoh F
    • Organizer
      10th Korea-Japan Joint Symposium on Vasuclar Biology
    • Place of Presentation
      Tokushima, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] endent miRNA pathway is important for early hematopoiesis but not for ang2011

    • Author(s)
      伊東史子
    • Organizer
      第19回血管生物医学会
    • Place of Presentation
      東京ステーションコンファレンス
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Involvement of TGF-β/Smad pathway in lymphangiogenesis2011

    • Author(s)
      伊東史子
    • Organizer
      JSPS-NOW Joint Seminar
    • Place of Presentation
      昭和薬科大学
    • Year and Date
      2011-11-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-β signaling is involved in lymphatic vessel development in vivo2011

    • Author(s)
      伊東史子
    • Organizer
      FASEB Summer Research Conference
    • Place of Presentation
      Luccaイタリア
    • Year and Date
      2011-08-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGF-βsignaling is involved in lymphatic vessel development in vivo2011

    • Author(s)
      Itoh, F., Itoh, S., Watanabe, T., and Kato, M
    • Organizer
      FASEB Summer Research Conference
    • Place of Presentation
      Lucca, Italia
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of TGF-β/Smad pathway in lymphangiogenesis2011

    • Author(s)
      Itoh, F., Ichikawa, K., Itoh, S., and Watanabe, T
    • Organizer
      JSPS-NOW Joint Seminar
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF-βsignaling controls tumor blood- and lymph angiogenesis.

    • Author(s)
      Itoh F, Takagi T, Ichikawa K, Fruttiger M, Oliver G, Watanabe T and Itoh S.
    • Organizer
      FASEB Summer Research conference, TGF-βsuperfamily: Signaling in Development and Disease.
    • Place of Presentation
      Steamboad springs, Colorad, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] The role of TGF-βsignaling in Tumor blood and Lymph angiogenesis

    • Author(s)
      Itoh F, Takagi T, Ichikawa K, Fruttiger M, Oliver G, Itoh S and Watanabe T.
    • Organizer
      The 3rd International Symposium by JSPS Core-to-Core Program “Cooperative International Frame work in TGF-β Family Signaling”
    • Place of Presentation
      Matsuyama, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] TGF-β signaling regulates lymphangiogenesis in vivo.

    • Author(s)
      Itoh F.
    • Organizer
      Gordon Research Conferences. Molecular Mechanisms in Lymphatic Function & Disease.
    • Place of Presentation
      Lucca (Barga), Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] GF-βシグナルは血管の恒常性維持に必須である.

    • Author(s)
      伊東史子、伊東進.
    • Organizer
      第9回麒麟塾
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The role of TGF-β signaling in blood- and lymph- angiogenesis.

    • Author(s)
      伊東史子
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 薬学のための分子生物学2014

    • Author(s)
      金田典雄、伊東進 編
    • Total Pages
      318
    • Publisher
      広川書店
    • Related Report
      2013 Annual Research Report
  • [Book] 血管新生と腫瘍血管.がんの増殖と悪性化の分子機構.宮澤恵二、伊東進編2013

    • Author(s)
      伊東史子
    • Publisher
      化学同人
    • Related Report
      2013 Final Research Report
  • [Book] 化学同人2012

    • Author(s)
      伊東史子
    • Publisher
      血管新生と腫瘍血管. がんの増殖と悪性化の分子機構 宮澤恵二、伊東進編
    • Related Report
      2012 Annual Research Report
  • [Book] TGF-βシグナル研究―メカニズムの解明からあらたな治療へ.別冊・医学のあゆみ2011

    • Author(s)
      伊東史子、加藤光保
    • Related Report
      2013 Final Research Report
  • [Book] 胚体外血管系と造血、血管生物医学事典2011

    • Author(s)
      伊東史子
    • Publisher
      朝倉書店
    • Related Report
      2013 Final Research Report
  • [Book] Smad、血管生物医学事典2011

    • Author(s)
      伊東史子
    • Publisher
      朝倉書店
    • Related Report
      2013 Final Research Report
  • [Book] 別冊・医学のあゆみTGF-βシグナル研究-メカニズムの解明からあらたな治療へ2011

    • Author(s)
      伊東史子
    • Total Pages
      5
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2011 Annual Research Report
  • [Book] 血管生物医学事典2011

    • Author(s)
      伊東史子
    • Total Pages
      4
    • Publisher
      朝倉書店
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] ミオスタチンインヒビター2014

    • Inventor(s)
      林良ほか
    • Industrial Property Rights Holder
      林良ほか
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-01-31
    • Related Report
      2013 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ミオスタチン阻害ペプチド2013

    • Inventor(s)
      林良雄ほか
    • Industrial Property Rights Holder
      林良雄ほか
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-017540
    • Filing Date
      2013-01-31
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] ミオスタチン阻害ペプチド2013

    • Inventor(s)
      林良雄、伊東史子ほか
    • Industrial Property Rights Holder
      林良雄、伊東史子ほか
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-017540
    • Filing Date
      2013-01-31
    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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