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Functional analysis of ADAM28 on cancer cells by bioluminescence imaging

Research Project

Project/Area Number 21590421
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKeio University

Principal Investigator

MOCHIZUKI Satsuki  慶應義塾大学, 医学部, 講師 (80365428)

Co-Investigator(Kenkyū-buntansha) OKADA Yasunori  慶應義塾大学, 医学部, 教授 (00115221)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsADAM / 癌転移 / VWF / アポトーシス / MMP / CTGF / 血管新生 / 乳癌 / バイオイメージング / 肺癌 / 転移 / 浸潤 / ルシフェラーゼ
Research Abstract

To explore the molecular mechanism of ADAM28/VWF-mediated metastasis, we established PC-9 lung carcinoma cells and MDA-MB231 breast carcinoma cells expressing Venus and luciferase(PC-9^<ffLuc-cp156> and MDA-MB231^<ffLuc-cp156> cells), and used them in the mouse models of lung metastasis, and primary tumor growth and spontaneous metastasis. Inhibition of ADAM28 expression with shRNA or siRNA and its inactivation with the neutralizing anti-ADAM28 antibody significantly reduced lung metastasis of PC-9^<ffLuc-cp156> cells and enhanced apoptosis of the cells within blood vessels. The primary tumor growth of ADAM28-shRNA transfectants after orthotopic implantation of MDA-MB231^<ffLuc-cp156> cells was significantly slower than that of mock-transfectants. By RT-PCR analysis for the expression of ffLuc-cp156 transcripts, metastasis in the lung, heart, liver, kidney and brain was reduced in the mice received ADAM28-shRNA transfectants as compared with mock-transfectants. Plasma samples from mice with injection of mock-transfected PC-9^<ffLuc-cp156> cells showed decreased amount of large VWF multimers as compared with those from mice which received ADAM28-shRNA transfectants or no cells. All these in vivo and in vitro data suggest that ADAM28 derived from carcinoma cells cleaves and inactivates pro-apoptotic endogenous agent VWF, thereby promotes the carcinoma cell survival within the blood stream and ultimately enhances their metastasis

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (34 results)

All 2012 2011 2010 2009 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (12 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Effect of ADAM28 on Carcinoma Cell Metastasis by Cleavage of von Willebrand Factor2012

    • Author(s)
      Satsuki Mochizuki, Kenji Soejima, Masayuki Shimoda, Hitoshi Abe, Aya Sasaki, Hirotaka James Okano, Hideyuki Okano, Yasunori Okada
    • Journal Title

      J. Natl. Cancer Inst

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory Role of Dendritic Cells in Post-Infarction Healing and Left Ventricular Remodeling2012

    • Author(s)
      Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Yuichiro Maekawa, Kotaro Naito, Hidehiro Kaneko, Yasuo Sugano, Toshiyuki Takahashi, Hitoshi Abe, Satsuki Mochizuki, Motoaki Sano, Tsutomu Yoshikawa, Yasunori Okada, Shigeo Koyasu, Satoshi Ogawa, and Keiichi Fukuda
    • Journal Title

      Circulation

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ADAM282012

    • Author(s)
      Satsuki Mochizuki and Yasunori Okada
    • Journal Title

      Handbook of Proteolytic Enzymes

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of ADAM28 on Carcinoma Cell Metastasis by Cleavage of von Willebrand Factor2012

    • Author(s)
      Satsuki Mochizuki
    • Journal Title

      Journal of the National Cancer Institute

      Volume: 104(In press) Issue: 12 Pages: 906-922

    • DOI

      10.1093/jnci/djs232

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Host-derived MMP-13 exhibits a protective role in lung metastasis of melanoma cells by local endostatin production2011

    • Author(s)
      Hiroki Fukuda, Satsuki Mochizuki, Hitoshi Abe, Hirotaka James Okano, Chikako Hara-Miyauchi, Hideyuki Okano, Noriko Yamaguchi, Mitsuo Nakayama, Jeanine D' Armiento and Yasunori Okada
    • Journal Title

      Br. J. Cancer

      Volume: 105 Pages: 1615-1624

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin 3A is expressed in human osteoarthritic cartilage and antagonizes vascular endothelial growth factor 165-promoted chondrocyte migration2011

    • Author(s)
      Masashi Okubo, Tokuhiro Kimura, Yoshinari Fujita, Satsuki Mochisuki, Yasuo Niki, Enomoto H, Yasunori Suda, Yoshiaki T and Yasunori Okada
    • Journal Title

      Arthritis Rheum

      Volume: 63 Pages: 3000-3009

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Host-derived MMP-13 exhibits a protective role in lung metastasis of melanoma cells by local endostatin production2011

    • Author(s)
      Hiroki Fukuda
    • Journal Title

      British Journal of Cancer

      Volume: 105 Issue: 10 Pages: 1615-1624

    • DOI

      10.1038/bjc.2011.431

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin 3A is expressed in human osteoarthritic cartilage and antagonizes vascular endothelial growth factor 165-promoted chond rocyte migration2011

    • Author(s)
      Masashi Okubo
    • Journal Title

      Arthritis & Rheumatism

      Volume: 63 Issue: 10 Pages: 3000-3009

    • DOI

      10.1002/art.30482

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAM282011

    • Author(s)
      Satsuki Mochizuki
    • Journal Title

      Handbook of Proteolytic Enzymes

      Volume: 3(In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Connective tissue growth factor is a substrate of ADAM282010

    • Author(s)
      Satsuki Mochizuki, Rena Tanaka, Masayuki Shimoda, Junko Onuma, Yutaka Fujii, Hiromitsu Jinno and Yasunori Okada
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 402 Pages: 651-657

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] ADAM28 is a serological and histochemical marker for non-small-cell lung cancers2010

    • Author(s)
      Hiroaki Kuroda, Satsuki Mochizuki, Masayuki Shimoda, Miyuki Chijiiwa, Kazunori Kamiya, Yotaro Izumi, Masazumi Watanabe, Hirohisa Horinouchi, Masahumi Kawamura, Koichi Kobayashi and Yasunori Okada
    • Journal Title

      Int. J. Cancer

      Volume: 127 Pages: 1844-1856

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Connective tissue growth factor is a substrate of ADAM282010

    • Author(s)
      Satsuki Mochizuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 402 Pages: 651-657

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAM28 is a serological and histochemical marker for non-small-cell lung cancers2010

    • Author(s)
      Hiroaki Kuroda
    • Journal Title

      International Journal of Cancer

      Volume: 127 Pages: 1844-1856

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAM28 is a serological and histochemical marker for non-small-cell lung cancers2010

    • Author(s)
      Hiroaki Kuroda
    • Journal Title

      International Journal of Cancer (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ADAM28 as therapeutic target2009

    • Author(s)
      Satsuki Mochizuki
    • Journal Title

      Current Pharmaceutical Design 15

      Pages: 2349-2358

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MMP-13 Plays a Role in Keratinocyte Migration, Angiogenesis, and Contraction in Mouse Skin Wound Healing2009

    • Author(s)
      Noriko Hattori
    • Journal Title

      American Journal of Pathology 175

      Pages: 533-546

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ADAM28による癌細胞転移機構2011

    • Author(s)
      望月早月、下田将之、岡田保典
    • Organizer
      弟9回日本エラスチン研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2011-12-02
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28 may promote VEGF165-induced angiogenesis in breast carcinomas by the CTGF digestion in the CTGF/VEGF165 complex2011

    • Author(s)
      Satsuki Mochizuki, Rena Tanaka, and Yasunori Okada
    • Organizer
      Gordon Research Conference on Matrix Metalloproteinase
    • Year and Date
      2011-08-10
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28 may promote VEGF165-induced angiogenesis in breast carcinomas by the CTGF digestion in the CTGF/VEGF165 complex2011

    • Author(s)
      Satsuki Mochizuki
    • Organizer
      Gordon Research Conference on Matrix Metal loproteinase
    • Place of Presentation
      Smithfield, USA
    • Year and Date
      2011-08-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] ADAM28のCTGF分解を介したCTGF/VEGF_<165>複合体からのVEGF_<165>の遊離と血管新生促進作用2011

    • Author(s)
      望月早月、田中伶奈、岡田保典
    • Organizer
      第20回がん転移学会学術集会・総会
    • Place of Presentation
      浜松
    • Year and Date
      2011-06-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 結合組織増殖因子(Connective tissue growth factor, CTGF)は、ADAM28の新規基質である2011

    • Author(s)
      望月早月、田中伶奈、岡田保典
    • Organizer
      第43回日本結合組織学会学術大会、第58回マトリックス研究会大会合同学術集会
    • Place of Presentation
      別府
    • Year and Date
      2011-06-11
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28のヒト癌細胞増殖・転移への関与と肺癌診断への応用2010

    • Author(s)
      望月早月、岡田保典
    • Organizer
      第42回日本結合組織学会学術大会、第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田
    • Year and Date
      2010-08-19
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28のヒト癌細胞増殖・転移への関与と肺癌診断への応用2010

    • Author(s)
      望月早月
    • Organizer
      第42回日本結合組織学術大会・第57回マトリックス研究会大会合同学術集会
    • Place of Presentation
      秋田拠点センター・アルヴェ(秋田)
    • Year and Date
      2010-08-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 癌細胞転移におけるADAM28の役割2010

    • Author(s)
      望月早月、下田雅之、岡田保典
    • Organizer
      第19回日本がん転移学会学術集会・総会
    • Place of Presentation
      金沢
    • Year and Date
      2010-06-16
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28によるvon Wiilebrand factorの分解と癌細胞転移2010

    • Author(s)
      望月早月
    • Organizer
      第17回プロテオグリカンフォーラム
    • Place of Presentation
      東京
    • Year and Date
      2010-02-27
    • Related Report
      2011 Final Research Report
  • [Presentation] ADAM28はVWF誘導性のアポトーシスを抑制し、癌細胞の浸潤・転移促進に働く2009

    • Author(s)
      望月早月、下田雅之、岡野洋尚、岡田保典
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] ADAM28 is involved in the invasion and metastasis of cancer cells by escaping from apoptosis through the cleavage of von Willebrand factor2009

    • Author(s)
      Satsuki Mochizuki, Masayuki Shimoda, Kenji Soejima, Hirotaka James Okano, Osahiko Tsuji, and Yasunori Okada
    • Organizer
      Gordon Research Conference on Matrix Metalloproteinase
    • Place of Presentation
      Les Diablerets
    • Year and Date
      2009-09-02
    • Related Report
      2011 Final Research Report
  • [Presentation] The role of ADAM28 in cancer cell proliferation and progression2009

    • Author(s)
      Satsuki Mochizuki, Masayuki Shimoda, Kenji Soejima, Rena Tanaka, Hirotaka James Okano, Osahiko Tsuji and Yasunori Okada
    • Organizer
      8^<th> Pan-Pacific Connective Tissue Society Symposium
    • Place of Presentation
      Yokosuka
    • Year and Date
      2009-06-05
    • Related Report
      2011 Final Research Report
  • [Book] 第1章MMP/TIMP pp66-68,第6章線維化pp458-460「日本血管生物医学事典」2011

    • Author(s)
      望月早月、岡田保典
    • Publisher
      朝倉書店
    • Related Report
      2011 Final Research Report
  • [Book] 日本血管生物医学事典2011

    • Author(s)
      望月早月
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://keio-okada-lab.jp/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://keio-okada-lab.jp/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://keio-okada-lab.jp/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://keio-okada-lab.jp/

    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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