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2013 Fiscal Year Final Research Report

Endogenous TLR4 ligands in tumor metastasis.

Planned Research

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Project AreaHomeostatic inflammation: Molecular basis and dysregulation
Project/Area Number 21117008
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Women's Medical University

Principal Investigator

MARU Yoshiro  東京女子医科大学, 医学部, 教授 (00251447)

Co-Investigator(Renkei-kenkyūsha) NAKAMURA Sachie  東京女子医科大学, 医学部, 准教授 (60313087)
TSUKAHARA Fujiko  東京女子医科大学, 医学部, 講師 (40119996)
TOMITA Takeshi  東京女子医科大学, 医学部, 助教 (20302242)
DEGUCHI Atsuko  東京女子医科大学, 医学部, 助教 (10422932)
IEGUCHI Katsuaki  東京女子医科大学, 医学部, 助教 (90586348)
TAKITA Morichika  東京女子医科大学, 医学部, 助教 (80533455)
Project Period (FY) 2009-07-23 – 2014-03-31
KeywordsTLR4 / SAA3 / S100A8 / CCL2 / ephrinA1 / 自然免疫 / がん転移
Research Abstract

We focused on five points (1)endogenous ligands for TLR4 (2)homeostasis inflammation (3)pathological condition (4)translational research, and (5)generation of knockout mice. We showed conclusion as below.
(1)We showed binding between TLR4/MD-2 and peptide SAA3 (20-86). Binding site of S100A8 was center domain of TLR4. (2)Bronchial Clara cells contribute to lung metastasis by amplifying SAA3. (3)We found that C1D, a DNA-binding protein, is a novel endogenous ligand for TLR9. We found that TLR4 signaling plays a role in resistance to BCR-ABL kinase inhibitor, imatinib, in Chronic myeloid leukemia. (4)We identified mTOC as a Cerastramycin binding protein. We created human SAA3 ELISA system to quantitate SAA3 protein in culture media. We are investigating whether KB-R7785, an ADAM12 inhibitor, effect on lung metastasis by reduction of cleaved form of ephrin-A1. (5)To examine the homeostasis inflammation related to S100A8 and SAA3, we are trying to establish knockout mouse system.

  • Research Products

    (20 results)

All 2014 2013 2012 2011 2010 2009 Other

All Journal Article (17 results) Presentation (1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] ADAM12-cleaved ephrin-A1 contributes to lung metastasis2014

    • Author(s)
      Ieguchi K, Tomita T, Omori T, Komatsu A, Deguchi A, Masuda J, Duffy S, Coulthard M, Boyd A, Maru Y
    • Journal Title

      Oncogene

      Volume: 33(17) Pages: 2179-2190

  • [Journal Article] Connexin43 Functions as a Novel Interacting Partner of Heat Shock Cognate Protein 702013

    • Author(s)
      Hatakeyama T, Dai P, Harada Y, Hino H, Tsukahara F,Maru Y, Otsuji E, Takamatsu T
    • Journal Title

      Sci Rep.

      Volume: 3 Pages: 2179

  • [Journal Article] Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci2013

    • Author(s)
      Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Tamura S, Murakami M, Kijima H, Miyake K, Aburatani H, Maru Y
    • Journal Title

      Nat Commun

      Volume: 4 Pages: 1853

  • [Journal Article] Serum Amyroid A3 binds MD-2 to activates p38 and NF-kB pathway in a MyD88-dependent manner2013

    • Author(s)
      Deguchi A, Tomita T, Omori T, Komatsu A, Ohto U, Takahashi S, Tanimura N, Akashi-Takamura S, Miyake K, Maru Y
    • Journal Title

      J Immunol. 2013

      Volume: 191, 4, 2013 Pages: 1856-1864

  • [Journal Article] Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 42013

    • Author(s)
      Ieguchi K, Omori T, Komatsu A, Tomita T, Deguchi A, Maru Y
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 440(4) Pages: 623-629

  • [Journal Article] Molecular biology of chronic myeloid leukemia2012

    • Author(s)
      Maru Y
    • Journal Title

      Cancer Sci.

      Volume: 103, 9 Pages: 1601-1610

  • [Journal Article] Endogenous ligand-induced activation of TLR4 in Pre-metastatic phase is both downstream and upstream of TNF signaling2011

    • Author(s)
      Maru Y
    • Journal Title

      Adv Exp Med Biol.

      Volume: 691 Pages: 261-268

  • [Journal Article] Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation2011

    • Author(s)
      Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, Jain RK
    • Journal Title

      Proc Natl Acad Sci USA.

      Volume: 108 Pages: 3725-3730

  • [Journal Article] Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis2011

    • Author(s)
      Tomita T, Sakurai Y, Ishibashi S, Maru Y
    • Journal Title

      Oncogene.

      Volume: 30 Pages: 3429-3439

  • [Journal Article] p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc702011

    • Author(s)
      Zou P, Yoshihara H, Hosokawa K, Tai I, Shinmyozu K, Tsukahara F, Maru Y, Nakayama K, Nakayama KI, Suda T
    • Journal Title

      Cell Stem Cell

      Volume: 9 Pages: 247-261

  • [Journal Article] XPB induces C1D expression to counteract UV-induced apoptosis2010

    • Author(s)
      Li G, Liu J, Abu-Asab M, Shibuya M, Maru Y
    • Journal Title

      Mol Cancer Res.

      Volume: 8 Pages: 885-895

  • [Journal Article] Pre-metastatic milieu explained by TLR4 agonist-mediated homeostatic inflammation2010

    • Author(s)
      Maru Y
    • Journal Title

      Cell and Mol Immun.

      Volume: 7 Pages: 94-99

  • [Journal Article] Bag1 directly routes immature BCR-ABL for proteasomal degradation2010

    • Author(s)
      Tsukahara F, Maru Y
    • Journal Title

      Blood.

      Volume: 116 Pages: 3582-3592

  • [Journal Article] The tumor suppressor LZTS2 functions through the cellular samurai Katanin2009

    • Author(s)
      Maru Y
    • Journal Title

      Cent Eur J Biol.

      Volume: 4 Pages: 1-10

  • [Journal Article] EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility2009

    • Author(s)
      Yamazaki T, Masuda J, Omori T, Usui R, Akiyama H, Maru Y
    • Journal Title

      J Cell Sci.

      Volume: 122 Pages: 243-255

  • [Journal Article] Logical structures extracted from metastasis experiments2009

    • Author(s)
      Maru Y
    • Journal Title

      Cancer Sci.

      Volume: 100 Pages: 2006-2013

  • [Journal Article] A Concept of Homeostatic Inflammation Provided by Endogenous TLR4 Agonists that Function Before and After Danger Signal for Metastasis2009

    • Author(s)
      Maru Y
    • Journal Title

      Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

      Volume: 8 Pages: 337-347

  • [Presentation] S100A8 amyloid A3 and TLR4 in tumor metastasis2012

    • Author(s)
      Maru Y
    • Organizer
      4th International Muenster Meeting on Danger Signaling in Autoinflammation
    • Place of Presentation
      Muenster, Germany
    • Year and Date
      20120400
  • [Book] がん転移先微小環境を「見直す」2012

    • Author(s)
      丸義朗
    • Total Pages
      8-11
    • Publisher
      ニューサイエンス社,東京,日本
  • [Remarks] 東京女子医科大学医学部薬理学教室

    • URL

      http://www.twmu.ac.jp/Basic/yakuri/

URL: 

Published: 2015-06-25  

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