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Prostanoid regulates premetastatic niche formation in lung cancers

Research Project

Project/Area Number 15K15056
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionKitasato University

Principal Investigator

Majima Masataka  北里大学, 医学部, 教授 (70181641)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords前転移ニッチェ / プロスタグランジン / EP3受容体 / SDF-1 / COX-2 / 樹状細胞 / リンパ節 / リンパ管新生 / 腫瘍 / リンパ節転移 / ケモカイン / EP3 / PG
Outline of Final Research Achievements

The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2-derived prostaglandin E2 (PGE2) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell-derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE2 receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3-dependent induction of SDF-1.

Report

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

    (16 results)

All 2017 2016 2015 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 7 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Prostaglandin E Receptors, EP3 and EP4 Facilitates Wound Healing and Lymphangiogenesis with Enhanced Recruitment of M2 Macrophages in Mice.2016

    • Author(s)
      Hosono K, Isonaka R, Kawakami T, Narumiya S, Majima M.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 10 Pages: e0162532-e0162532

    • DOI

      10.1371/journal.pone.0162532

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Suppression of lymphangiogenesis by soluble vascular endothelial growth factor receptor-2 in a mouse lung cancer model.2016

    • Author(s)
      Maehana S, Nakamura M, Ogawa F, Imai R, Murakami R, Kojima F, Majima M, Kitasato H.
    • Journal Title

      Biomed Pharmacother.

      Volume: 84 Pages: 660-665

    • DOI

      10.1016/j.biopha.2016.09.083

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in mice.2016

    • Author(s)
      Kawashima-Takeda N, Ito Y, Nishizawa N, Kawashima R, Tanaka K, Tsujikawa K, Watanabe M, Majima M.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 32 Issue: 4 Pages: 809-818

    • DOI

      10.1111/jgh.13505

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Thromboxane A synthase enhances blood flow recovery from hindlimb ischemia.2016

    • Author(s)
      Amano H, Nakamura M, Ito Y, Kakutani H, Eshima K, Kitasato H, Narumiya S, Majima M.
    • Journal Title

      J Surg Res.

      Volume: 204 Issue: 1 Pages: 153-163

    • DOI

      10.1016/j.jss.2016.04.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils2016

    • Author(s)
      Kojo, K., Ito, Y., Eshima, K., Nishizawa, N., Ohkubo, H., Yokomizo, T., Shimizu, T., Watanabe, M.,Majima, M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 29650-29650

    • DOI

      10.1038/srep29650

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascular Endothelial Growth Factor Receptor Type 1 Signaling Prevents Delayed Wound Healing in Diabetes by Attenuating the Production of IL-1β by Recruited Macrophages.2016

    • Author(s)
      Okizaki S, Ito Y, Hosono K, Oba K, Ohkubo H, Kojo K, Nishizawa N, Shibuya M, Shichiri M, Majima M.
    • Journal Title

      Am J Pathol.

      Volume: 186 Issue: 6 Pages: 1481-1498

    • DOI

      10.1016/j.ajpath.2016.02.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Vascular Endothelial Growth Factor Receptor Type 1 Signaling Prevents Delayed Wound Healing in Diabetes by Attenuating the Production of IL-1β by Recruited Macrophages.2016

    • Author(s)
      Okizaki S, Ito Y, Hosono K, Oba K, Ohkubo H, Kojo K, Nishizawa N, Shibuya M, Shichiri M, Majima M.
    • Journal Title

      Am J Pathol.

      Volume: 186 Pages: 1481-1498

    • DOI

      10.1016/j.biopha.2016.01.005

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immune-mediated hepatitis.2016

    • Author(s)
      Fujita T, Soontrapa K, Ito Y, Iwaisako K, Moniaga CS, Asagiri M, Majima M, Narumiya S.
    • Journal Title

      Hepatology

      Volume: 63 Issue: 4 Pages: 1325-1339

    • DOI

      10.1002/hep.28112

    • NAID

      120005663256

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PDGFRα plays a crucial role in connective tissue remodeling.2015

    • Author(s)
      Horikawa S, Ishii Y, Hamashima T, Yamamoto S, Mori H, Fujimori T, Shen J, Inoue R, Nishizono H, Itoh H, Majima M, Abraham D, Miyawaki T, Sasahara M.
    • Journal Title

      Scientific Reports

      Volume: Dec 7;5 Issue: 1 Pages: 17948-17948

    • DOI

      10.1038/srep17948

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model.2015

    • Author(s)
      Matsuda H, Hosono K, Tsuru S, Kurashige C, Sekiguchi K, Akira S, Uematsu S, Okamoto H, Majima M.
    • Journal Title

      Life Sci.

      Volume: 142 Pages: 1-7

    • DOI

      10.1016/j.lfs.2015.10.008

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] An inducible mPGES-1 promotes lung metastasis via SDF-1/CXCR4-mediated recruitment of MDSCs2017

    • Author(s)
      Hideki Amano, Ryo Takahashi, Masataka Majima
    • Organizer
      第90回日本薬理学会年会 シンポジウム
    • Place of Presentation
      長崎 ブリックホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Roles of RAMP-1 Signalling as a Neuronal Cue of Lymphangiogenesis2016

    • Author(s)
      Masataka Majima
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Ventura, CA, USA
    • Year and Date
      2016-03-20
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal Cue for Neovascularization; CGRP-RAMP1 Signaling2015

    • Author(s)
      Masataka Majima
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      Newport, RI, USA
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] NEW薬理学第7版2017

    • Author(s)
      馬嶋正隆
    • Publisher
      南江堂
    • Related Report
      2016 Annual Research Report
  • [Book] 標準薬理学第7版、第23章 免疫炎症系2015

    • Author(s)
      馬嶋正隆
    • Total Pages
      50
    • Publisher
      医学書院
    • Related Report
      2015 Research-status Report
  • [Remarks] 北里大学医学部薬理学単位

    • URL

      http://www.med.kitasato-u.ac.jp/pharm/

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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