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Dissecting molecular mechanisms mediating human breast cancer metastasis

Research Project

Project/Area Number 24300332
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionJuntendo University

Principal Investigator

orimo akira  順天堂大学, 医学(系)研究科(研究院), 准教授 (70275866)

Co-Investigator(Kenkyū-buntansha) SAITO Mitsue  順天堂大学, 医学部, 教授 (30205679)
HORIMOTO Yoshiya  順天堂大学, 医学部, 准教授 (40424246)
小坂 泰二郎  順天堂大学, 医学部, 助教 (40398681)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords癌微小環境 / 癌転移 / CAFs / 細胞接着 / CAFs / 転移 / 癌浸潤・転移 / 浸潤・転移 / 乳癌 / 癌内線維芽細胞 / 上皮間葉移行
Outline of Final Research Achievements

CAFs predominantly present within the tumor-associated stroma. However, roles of CAFs on tumor malignancy haven’t fully understood yet at molecular levels. The invasion-metastatic cascade is composed of a series of multi-step processes and epi/genetic alterations are believed to be largely responsible for ability of cancer cells to metastasize. Recent emerging evidence also supports the notion that cancer metastasis depends on non-cell autonomous effect of nearby stromal cells. Here we show that CAFs induce highly metastatic ability into barely metastatic breast cancer cells via conferring self-stimulating autocrine signaling mediated by some cell adhesion molecules. These factors importantly promote cell-cell adhesions in carcinoma cells that can facilitate their metastatic dissemination and associated with poorer outcome in breast cancer patients. Taken together, these findings strongly suggest crucial roles of CAFs on promotion of tumor malignancy.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (29 results)

All 2016 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Book (6 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer.2016

    • Author(s)
      Englund E, Bartoschek M, Reitsma B, Jacobsson L, Escudero-Esparza A, Orimo A, Leandersson K, Hagerling C, Aspberg A, Storm P, Okroj M, Mulder H, Jirström K, Pietras K, Blom AM.
    • Journal Title

      Oncogene

      Volume: 11 Pages: 1-1

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The human complement inhibitor Sushi Domain-Containing Protein 4 (SUSD4) expression in tumor cells and CD8+ T cells is associated with better prognosis of breast cancer patients.2015

    • Author(s)
      Englund E, Reitsma B, King BC, Escudero-Esparza A, Owen S, Orimo A, Okroj M, Anagnostaki L, Jiang WG, Jirström K, Blom AM.
    • Journal Title

      BMC Cancer,

      Volume: 19 Pages: 737-737

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The human complement inhibitor Sushi Domain-Containing Protein 4 (SUSD4) expression in tumor cells and CD8+ T cells is associated with better prognosis of breast cancer patients.2015

    • Author(s)
      Englund E, Reitsma B, King BC, Escudero-Esparza A, Owen S, Orimo A, Okroj M, Anagnostaki L, Jiang WG, Jirström K, Blom AM
    • Journal Title

      BMC Cancer,

      Volume: 19 Pages: 737-737

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Carcinoma Associated Fibroblasts2013

    • Author(s)
      Polanska, Y. * and Orimo, A
    • Journal Title

      Journal of Cellular Physiology

      Volume: 228, Pages: 1651-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carcinoma-associated fibroblasts (CAFs) are a promising therapeutic target.2013

    • Author(s)
      Togo, S.*, Polanska, Y., Horimoto, Y and Orimo, A
    • Journal Title

      Cancers

      Volume: 5 Pages: 149-169

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TGF-β : guardian of catabolic metabolism in carcinoma-associated fibroblasts (CAFs).,2013

    • Author(s)
      Khan H. and Orimo A
    • Journal Title

      Cell Cycle

      Volume: 11 Pages: 4-5

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging roles of the tumour-associated stroma in promoting tumour metastasis.,2012

    • Author(s)
      Horimoto, Y., Takahashi, T., Polanska, Y. and Orimo, A.
    • Journal Title

      Cell adhesion and migration,

      Volume: 6 Pages: 193-202

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Carcinoma-associated fibroblasts confer adherent epithelial cell traits in breast cancer cells to promote metastasis2015

    • Author(s)
      Orimo A
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 癌細胞と癌内線維芽細胞の共進化および癌悪性化2015

    • Author(s)
      Orimo A
    • Organizer
      第30回発癌病理研究会
    • Place of Presentation
      小豆島
    • Year and Date
      2015-08-27
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 肺線維症研究の最前線 線維化と癌悪性化2015

    • Author(s)
      折茂彰
    • Organizer
      第12回肺研究フォーラム21
    • Place of Presentation
      東京
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 癌悪性化における癌内線維芽細胞の関与2015

    • Author(s)
      折茂彰
    • Organizer
      平成26年度「個体レベルでのがん研究支援活動」ワークショップ
    • Place of Presentation
      滋賀県大津市
    • Year and Date
      2015-02-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 癌内線維芽細胞による癌悪性化分子機構2015

    • Author(s)
      折茂彰
    • Organizer
      日本癌学会シンポジウム・共同利用共同研究拠点シンポジウム 「がん幹細胞・微小環境・分子標的〜がん進展制御への挑戦」
    • Place of Presentation
      金沢
    • Year and Date
      2015-01-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Carcinoma-associated fibroblasts educate incipient human mammary carcinoma cells to become invasive and metastatic. Symposia 10「Molecular pathophysiology of tumor microenvironment2012

    • Author(s)
      折茂彰, 他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Carcinoma-associated fibroblasts confer metastatic abilities into apposed human mammary carcinoma cells.

    • Author(s)
      Akira Orimo, 他5名(6人中1番目)
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evolution of metastasis-promoting myofibroblasts in the tumour-associated stroma.

    • Author(s)
      折茂 彰
    • Organizer
      第19回文京脳腫瘍研究会
    • Place of Presentation
      東京ガーデンパレスホテル
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Evolution of metastasis-promoting stromal myofibroblasts.

    • Author(s)
      折茂 彰
    • Organizer
      58回幹細胞治療研究センターフォーラム
    • Place of Presentation
      東京大学医科学研究所
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Jagged1-stimulated Notch3 signalling activation in carcinoma-associated fibroblasts mediates their activated tumour-promoting trait.

    • Author(s)
      Akira Orimo, 他6名(7人中7番目)
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] The development of gross hepatic and pulmonary metastases in a patient-derived colorectal tumor xenograft mode

    • Author(s)
      Akira Orimo,
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Book] 実験医学2016

    • Author(s)
      折茂彰
    • Total Pages
      141
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Book] 呼吸2016

    • Author(s)
      伊藤匠、松村優子、伊藤恭彦、折茂彰
    • Total Pages
      94
    • Publisher
      呼吸研究
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Book] 実験医学2015

    • Author(s)
      折茂彰, 松村優子,本多一貴, Nadila Wali
    • Total Pages
      210
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Book] 呼吸器内科2015

    • Author(s)
      折茂彰, 松村優子,伊藤恭彦,十合晋作
    • Total Pages
      87
    • Publisher
      科学評論社
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Book] 肺の損傷と発癌機序「Annual Review呼吸器20152015

    • Author(s)
      谷口源太郎、折茂彰
    • Total Pages
      258
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Book] 細胞工学2014

    • Author(s)
      松村優子,伊藤恭彦,折茂彰
    • Total Pages
      586
    • Publisher
      学研メディカル秀潤社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 文部科学省科学研究費新学術領域―がん研究分野の特性等を踏まえた支援活動 研究紹介

    • URL

      http://ganshien.umin.jp/research/main/orimo/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 癌転移を促進する癌間質のしくみを探る

    • URL

      http://ganshien.umin.jp/research/main/orimo/index.html

    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 強転移性ヒト癌細胞株2013

    • Inventor(s)
      折茂 彰
    • Industrial Property Rights Holder
      折茂 彰
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-08-30
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 早期癌転移検出法および新規癌転移抑制薬のスクリーニング法2013

    • Inventor(s)
      折茂 彰
    • Industrial Property Rights Holder
      折茂 彰
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-12
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒト癌上皮細胞の遠隔転移のモデルマウス作出方法2012

    • Inventor(s)
      折茂彰
    • Industrial Property Rights Holder
      折茂彰
    • Filing Date
      2012-08-08
    • Related Report
      2012 Annual Research Report

URL: 

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

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