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Molecular analysis of metastasis-related tumor microenvironment and development of new anti-metastatic therapy

Planned Research

Project AreaIntegrative Research on Cancer Microenvironment Network
Project/Area Number 22112008
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 InstitutionJapanese Foundation for Cancer Research

Principal Investigator

FUJITA Naoya  公益財団法人がん研究会, がん化学療法センター, 所長 (20280951)

Co-Investigator(Kenkyū-buntansha) OGO Naohisa  静岡県立大学, 薬学研究院・創薬探索センター, 講師 (20501307)
Research Collaborator SATO Shigeo  
NAKAZAWA Youya  
MISAWA Aya  
TAKEMOTO Ai  
OH-HARA Tomoko  
TAKAMI Miho  
MIYATA Kenichi  
OKITAKA Mina  
SEKIGUCHI Takaya  
TAKATORI Kazuki  
FUSE Miho Jane  
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥86,060,000 (Direct Cost: ¥66,200,000、Indirect Cost: ¥19,860,000)
Fiscal Year 2014: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2013: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2012: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2011: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2010: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
Keywords癌 / がん微小環境 / 転移 / Merm1 / 血小板 / 微小環境 / 細胞死 / がん転移 / 血小板凝集 / 生体分子
Outline of Final Research Achievements

In this project, we tried to analyze the regulation of metastasis-promoting activities of Merm1 and Aggrus by tumor microenvironment and to develop anti-metastatic drugs. We performed the following experiments and obtained several new findings.
(1) We found that Merm1 enhanced tumor cell survival in the vasculature by suppressing p53-mediated apoptosis. We established the in vivo screening system to select high metastatic tumors and obtained several candidate metastasis-related genes.
(2) We analyzed the role of platelets in tumor growth and metastasis. We found that platelets were one of the components of tumor microenvironment, that growth factors secreted from platelets were associated with tumor growth in vivo, and that anti-Aggrus drugs would suppress tumor growth as well as tumor metastasis.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (45 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (21 results) (of which Invited: 5 results) Remarks (4 results)

  • [Journal Article] Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment.2014

    • Author(s)
      Kenichi Miyata, Satoshi Takagi, Shigeo Sato, Hiroshi Morioka, Kiyotaka Shiba, Tamiko Minamisawa, Miho Takami, and Naoya Fujita
    • Journal Title

      Cancer Med.

      Volume: 3 Issue: 6 Pages: 1595-1604

    • DOI

      10.1002/cam4.320

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Platelets promote osteosarcoma cell growth through activation of the PDGFR-Akt signaling axis.2014

    • Author(s)
      Satoshi Takagi, Ai Takemoto, Miho Takami, Tomoko Oh-hara, and Naoya Fujita
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 8 Pages: 983-988

    • DOI

      10.1111/cas.12464

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Adhesion of pancreatic cancer cells in a liver-microvasculature mimicking co-culture correlates with their propensity to form liver-specific metastasis in vivo.2014

    • Author(s)
      Mohammad Mahfuz Chowdhury, Mathieu Danoy, Farhana Rahman, Marie Shinohara, Shohei Kaneda, Kiyotaka Shiba, Naoya Fujita, Teruo Fujii and Yasuyuki Sakai
    • Journal Title

      BioMed Research International

      Volume: 241571 Pages: 1-13

    • DOI

      10.1155/2014/241571

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis2014

    • Author(s)
      Takagi S, Oh-hara T, Sato S, Gong B, Takami M, Fujita N.
    • Journal Title

      International Journal of Cancer

      Volume: 134 Issue: 11 Pages: 2605-2614

    • DOI

      10.1002/ijc.28602

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adhesion of pancreatic cancer cells in a liver-microvasculature mimicking co-culture correlates with their propensity to form liver-specific metastasis in vivo.2014

    • Author(s)
      Chowdhury MM, Danoy M, Rahman F, Shinohara M, Kaneda S, Shiba K, Fujita N, Fujii T, Sakai Y.
    • Journal Title

      BioMed Res. Int.

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2.2013

    • Author(s)
      Takagi S, Sato S, Oh-hara T, Takami M, Koike S, Mishima Y, Hatake K, Fujita N.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 8 Pages: e73609-e73609

    • DOI

      10.1371/journal.pone.0073609

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition2013

    • Author(s)
      Katayama R, Aoyama A, Yamori T, Qi J, Oh-Hara T, Song Y, Engelman JA, Fujita N
    • Journal Title

      Cancer Res

      Volume: 73(10) Issue: 10 Pages: 3087-96

    • DOI

      10.1158/0008-5472.can-12-3256

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR activating and gatekeeper mutations.2013

    • Author(s)
      Yamada T, Yano S, et al.
    • Journal Title

      Oncogene

      Volume: 32 Issue: 37 Pages: 4427-35

    • DOI

      10.1038/onc.2012.446

    • NAID

      120004997024

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of Aggrus/podoplanin on platelet aggregation and tumor metastasis.2012

    • Author(s)
      Fujita, N., et al.
    • Journal Title

      J Biochem.

      Volume: 152 Issue: 5 Pages: 407-413

    • DOI

      10.1093/jb/mvs108

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro2012

    • Author(s)
      Jens Hahne
    • Journal Title

      Oncology Reports

      Volume: 28 Issue: 6 Pages: 2023-2028

    • DOI

      10.3892/or.2012.2041

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successive phosphorylation of p27^<KIP1> protein at serine-10 and C terminus crucially controls its potency to inactivate Cdk2.2012

    • Author(s)
      Atish R. Mohanty
    • Journal Title

      Journal of Biological Chemistry

      Volume: 287 Issue: 26 Pages: 21757-21764

    • DOI

      10.1074/jbc.m112.346254

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of hematogenous metastasis by neutralizing mice and its chimeric anti-Aggrus/podoplanin antibodies2011

    • Author(s)
      Nakazawa Y, Fujita N, et al
    • Journal Title

      Cancer Science

      Volume: 102 Issue: 11 Pages: 2051

    • DOI

      10.1111/j.1349-7006.2011.02058.x

    • NAID

      10030245233

    • URL

      https://localhost/en/publications/3380de80-5934-4516-b7db-215739f22643

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis.2011

    • Author(s)
      Youya Nakazawa
    • Journal Title

      Cancer Res.

      Volume: 71 Pages: 1146-1155

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers.2011

    • Author(s)
      Sayuri Konishi
    • Journal Title

      In Vitro Cell.Dev.Biol.Anim.

      Volume: 47 Pages: 45-53

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell-permeable carboxy-terminal p27^<Kip1> peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase.2011

    • Author(s)
      Daisuke Morishita
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 2681-2688

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells.2011

    • Author(s)
      Shogo Ehata
    • Journal Title

      Oncogene

      Volume: 30 Pages: 1693-1705

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-stimulated interaction with 14-3-3 promotes cytoplasmic localization of lipin-1 in adipocytes.2010

    • Author(s)
      Miklos Peterfy
    • Journal Title

      J.Biol.Chem.

      Volume: 285 Pages: 3857-3864

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitotic phosphorylation of Akil at Ser^<208> by cyclin B1-Cdk1 complex.2010

    • Author(s)
      Akito Nakamura
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 393 Pages: 872-876

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AP-1-dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells.2010

    • Author(s)
      Aya Misawa
    • Journal Title

      Oncol.Res.

      Volume: 19 Pages: 23-33

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of Wnt signaling by the nuclear localization of cellular FLIP-L.2010

    • Author(s)
      Ryohei Katayama
    • Journal Title

      J.Cell Sci.

      Volume: 123 Pages: 23-28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 血小板によるがんの増殖と転移の促進2015

    • Author(s)
      藤田直也
    • Organizer
      Recent Advance in Tumor Angiogenesis 2014
    • Place of Presentation
      グランドホテル浜松、浜松
    • Year and Date
      2015-01-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Aggrus-induced platelet aggregation promotes tumor metastasis by enhancing EMT.2015

    • Author(s)
      Ai Takemoto, Satoshi Takagi, Mina Okitaka, Miho Takami, Shigeo Sato, Tomoko Oh-hara, and Naoya Fujita
    • Organizer
      Joint International Symposium on TGF-β and Cancer
    • Place of Presentation
      つくば国際会議場、つくば
    • Year and Date
      2015-01-12 – 2015-01-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis2014

    • Author(s)
      大原智子、高木聡、竹本愛、佐藤重男、高見美穂、藤田直也
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Platelets promote the malignancy of osteosarcoma through activation of the PDGFR-Akt signaling2014

    • Author(s)
      竹本愛、高木聡、高見美穂、大原智子、藤田直也
    • Organizer
      第73回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 一本鎖抗体によるAggrus/podoplanin依存的な血小板凝集及び肺転移の抑制2014

    • Author(s)
      宮田憲一、高木聡、藤田 直也
    • Organizer
      第23回日本がん転移学会
    • Place of Presentation
      金沢市文化ホール、金沢
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規血小板凝集促進因子Aggrusを標的とした分子標的2014

    • Author(s)
      藤田直也
    • Organizer
      平成25年度彩都産学官連携シンポジウム
    • Place of Presentation
      千里ライフサイエンスセンター、大阪
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Development of anti-Aggrus/podoplanin antibodies suppressing hematogenous metastasis and tumor growth in vivo2013

    • Author(s)
      藤田直也、高木聡
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Suppression of tumor growth in vivo by a murine/human chimeric anti-Aggrus neutralizing antibody2013

    • Author(s)
      高木聡、佐藤重男、藤田直也
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜、横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Aggrus/podoplaninを標的とした中和抗体による抗転移効果と抗腫瘍効果2013

    • Author(s)
      高木聡、藤田直也
    • Organizer
      第22回日本がん転移学会学術集会
    • Place of Presentation
      ホテルブエナビスタ、松本
    • Related Report
      2013 Annual Research Report
  • [Presentation] Aggrus/PodoplaninはRho/ROCKシグナルを活性化し胸膜中皮腫の進展を促進する2013

    • Author(s)
      竹内伸司 山田忠明 藤田直也 石井源一郎 落合淳志 矢野聖二
    • Organizer
      第53回 日本呼吸器学会学術講演会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Targeting tumor-host interaction for developing anti-metastatic therapies.2012

    • Author(s)
      Naoya Fujita
    • Organizer
      JST CREST/SICP/ERATO Joint Symposium on " Microfluidics for Tissue and Cell Applications"
    • Place of Presentation
      東京大学、東京
    • Year and Date
      2012-11-05
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The role of tumor-platelet interaction in hematogenous metastasis.2012

    • Author(s)
      Naoya Fujita
    • Organizer
      The 2nd International Symposium by JSPS Core-to-Core Program "TGF-β Family: Signal Network and Tumor Microenvironment"
    • Place of Presentation
      昭和薬科大学、東京
    • Year and Date
      2012-10-29
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Involvement of platelet-tumor interaction in tumor cell survival and metastasis.2012

    • Author(s)
      Naoya Fujita
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌、札幌
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Role of Aggrus/podoplanin-induced platelet aggregation in tumor growth and metastasis formation.2012

    • Author(s)
      Naoya Fujita
    • Organizer
      The 9th Nikko International Symposium 2012 "Understanding complex network system in disease biology"
    • Place of Presentation
      自治医科大学、栃木
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] がん分子標的の探索から治療薬開発への展開とその現状2011

    • Author(s)
      藤田直也
    • Organizer
      第141回日本医学会シンポジウム
    • Place of Presentation
      日本医師会館大講堂、東京(招待講演)
    • Year and Date
      2011-12-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Prevention of hematogenous metastasis by mouse and murine/human chimeric anti-Aggrus/podoplanin antibodies2011

    • Author(s)
      高木聡
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋国際会議場、名古屋
    • Year and Date
      2011-10-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血小板凝集促進因子Aggrusを標的とした抗体による血行性転移の阻害2011

    • Author(s)
      高木聡
    • Organizer
      第20回日本がん転移学会
    • Place of Presentation
      アクトシティ浜松、浜松
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel histone methyltransferase Merm1 promotes metastasis by Zac1 silencing.2010

    • Author(s)
      Youya Nakazawa
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] AP-1-dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells.2010

    • Author(s)
      Aya Misawa
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Overexpression of multidrug resistance-associated protein-2 (mrp2/ABCC2) contributes chemoresistance in breast cancer stem-like SP cells.2010

    • Author(s)
      Sumie Koike
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] p27kip1 carboxy-terminal derived peptide possesses anti-tumor activity by inhibiting proto-oncogene pim-1 kinase.2010

    • Author(s)
      Daisuke Morishita
    • Organizer
      第69回日本癌学会総会
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Remarks] 公益財団法人がん研究会がん化学療法センター基礎研究部ホームページ

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/fundamental/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] (公財)がん研究会がん化学療法センター基礎研究部

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/fundamental/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/fundamental/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.jfcr.or.jp/chemotherapy/department/fundamental/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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