ADAM28 cleaves von Willebrand factor and induces cancer cell metastasis

• Project/Area Number: 19590404
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Keio University
• Principal Investigator: SATSUKI Mochizuki Keio University, 医学部, 助教 (80365428)
• Co-Investigator(Kenkyū-buntansha): OKADA Yasunori 慶應義塾大学, 医学部, 教授 (00115221)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: MMP / ADAM / vWF / 癌転移 / von Willebrand factor / 癌細胞増殖 / ADAMTS / アポトーシス / Yeast two-hybrid / 癌浸潤・転移 / 細胞外マトリックス / Yeast two-hybrid法 / 癌細胞の増殖

Research Abstract

ADAM28は乳癌や肺癌組織で高発現する分子であるが、その機能はよくわかっていない。本研究では、酵母two-hybrid法を用いてADAM28の新規基質としてvon Willebrandfactor(vWF)を見出した。さらに癌細胞で高発現するADAM28が血中でvWFと結合し分解することにより、癌細胞はvWF誘導のアポトーシスから回避され癌細胞浸潤転移が促進することが明らかとなった。

Research Products

• [Journal Article] ADAM28 as therapeutic target (2009)
  • Author(s): Satsuki Mochizuki and Yasunori Okada
  • Journal Title: Curr. Pharm. Design In press
  • Peer Reviewed
• [Journal Article] RANKL expression in clear cell renal cel carcinomas andits association with bone metastasis and cancer cell migration (2009)
  • Author(s): Shuji Mikami, Ken-ichi Katsube, MototsuguOya, Satsuki Mochizuki, Masayuki Shimoada, Ryuichi Mizuno, Masaru Ishida, Tohru Ikeda, Makio Mukai, and Yasunori Okada
  • Journal Title: J. Urology (In press)
• [Journal Article] Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic chondrocytes (2009)
  • Author(s): Taku Yatabe, Satsuki Mochizuki, Masayuki Takizawa, Miyuki Chijiiwa, Aiko Okada, Tokuhiro Kimura, Yoshinari Fujita, Hideo Matsumoto, Yoshiaki Toyama and Yasunori Okada
  • Journal Title: Ann. Rheum. Dis 68 Pages: 1051-1058
  • Peer Reviewed
• [Journal Article] ADAM28 as a Target for Human Cancer (2009)
  • Author(s): 望月 早月(1番目/2名)
  • Journal Title: Current Parmaceutical Design (In press)
  • Peer Reviewed
• [Journal Article] Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1)in human osteoarthritic chondrocytes (2009)
  • Author(s): 谷田部 拓, (望月早月 : 2番目/10名)
  • Journal Title: Annals of the Rheumatic Diseases (In press)
  • Peer Reviewed
• [Journal Article] Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aagrecanase-1) in osteoarthritic chondrocyte (2008)
  • Author(s): Masayuki Takizawa, Taku Yatabe, Aiko Okada, Miyuki Chijiiwa, Satsuki Mochizuki, Peter Ghosh and Yasunori Okada
  • Journal Title: FEBS Lett 582 Pages: 2945-2949
  • Peer Reviewed
• [Journal Article] ADAM-12 (meltrin-α) is involved in chondrocyte proliferation via cleavage of insulin-like growth factor binding protein 5 in osteoarthritic cartilage (2008)
  • Author(s): Aiko Okada, Satsuki Mochizuki, Taku Yatabe, Tokuhiro Kimura, Takayuki Shiomi, Yoshinari Fujita, Hideo Matsumoto, Atsuko Sehara-Fujisawa, Yukihide Iwamoto, Yasunori Okada
  • Journal Title: Arthritis Rhum 58 Pages: 778-789
  • Peer Reviewed
• [Journal Article] Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aagrecanase-1)in osteoarthritic chondrocyte (2008)
  • Author(s): 滝沢 雅之, (望月早月 : 5番目/7名)
  • Journal Title: FEBS Letter 582 Pages: 2945-2949
  • Peer Reviewed
• [Journal Article] ADAM-12(meltrin-α)is involved in chondrocyte proliferation via cleavage of insulin-like growth factor binding Protein 5 in osteoarthritic cartilage (2008)
  • Author(s): 岡田 愛子(望月 早月:2番目/10名)
  • Journal Title: Arthritis&Rhumatsm 58 Pages: 778-789
  • Peer Reviewed
• [Journal Article] Binding of ADAM28 to P-selectin glycoprotein ligand-1 enhances P-selectin-mediated leukocyte adhesion to endothelial cells (2007)
  • Author(s): Masayuki Shimoda, Gakuji Hashimoto, Satsuki Mochizuki, Eiji Ikeda, Norihiro Nagai, Susumu Ishida and Yasunori Okada
  • Journal Title: J. Biol. Chem 282 Pages: 25864-25874
  • Peer Reviewed
• [Journal Article] ADAMs in cancer cell proliferation and progression (2007)
  • Author(s): Satsuki Mochizuki and Yasunori Okada
  • Journal Title: Cancer Sci 98 Pages: 621-628
  • Peer Reviewed
• [Journal Article] ADAMs in cancer cell proliferation and progression (2007)
  • Author(s): 望月 早月
  • Journal Title: Cancer Science 282 Pages: 25864-25874
  • Peer Reviewed
• [Journal Article] Binding of ADAM28 to P-selectin glycoprotein ligand-1 enhances P-selectin-mediated leukocvte adhesion to endothelial cells (2007)
  • Author(s): 下田 将之(望月 早月:3番目/7名)
  • Journal Title: Journal of Biological Chemistry 282 Pages: 25864-25874
  • Peer Reviewed
• [Presentation] ADAM28による癌細胞の増殖・浸潤・転移 (2008)
  • Author(s): 望月早月、下田雅之、副島見事、岡田保典
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] ADAM28による癌細胞の増殖・浸潤・転移 (2008)
  • Author(s): 望月 早月
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] ADAM28 may promote cancer cell metastasis by preventing apoptosis through cleavage of von Willebrand factor (2008)
  • Author(s): Satsuki Mochizuki, Kenji Soejima, Masayuki Shimoda and Yasunori Okada
  • Organizer: The 6^<th> International Symposium on Cancer Research and Therapy
  • Place of Presentation: Tokyo
  • Year and Date: 2008-11-22
• [Presentation] ADAM28 may promote cancer cell metastasis by preventing apoptosis through cleavage of von Willebrand factor (2008)
  • Author(s): 望月 早月
  • Organizer: The 6^<th> International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京
  • Year and Date: 2008-11-22
• [Presentation] Analysis of ADAM28-interacting protein that may be related to cancer cell invasion and metastasis : ADAM28 directly binds to and cleaves von Willebrand factor (2008)
  • Author(s): Satsuki Mochizuki, Kenji Soejima, Masayuki Shimoda and Yasunori Okada
  • Organizer: FECTS XXIst Meeting
  • Place of Presentation: Marseille
  • Year and Date: 2008-07-13
• [Presentation] Analysis of ADAM28-interacting proteins that may be related to cancer cell invasion and metastasis : ADAM28 directly binds to and cleaves von Willebrand factor (2008)
  • Author(s): 望月 早月
  • Organizer: FECTS XXIst Meeting
  • Place of Presentation: マルセイユ(フランス)
  • Year and Date: 2008-07-13
• [Presentation] 癌細胞の浸潤・転移に関わるADAM28の結合蛋白質及び新規基質の探索 (2008)
  • Author(s): 望月早月、副島見事、下田将之、岡田保典
  • Organizer: 第40回日本結合組織学会学術大会・第55回マトリックス研究会大会合同学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-29
• [Presentation] High molecular weight hyaluronan inhibits ADAMTS4 (aggrecanase-1) expression through the CD44 signaling pathway in human osteoarthritic chondrocytes (2007)
  • Author(s): Taku Yatabe, Satsuki Mochizuki, Masayuki Takizawa, Miyuki Chijiiwa, Aiko Okada, Tokuhiro Kimura, Yoshinari Fujita, Hideo Matsumoto, Yoshiaki Toyama and Yasunori Okada
  • Organizer: 7th Pan Pacific Connective Tissue Societies Symposium
  • Place of Presentation: Cairns
  • Year and Date: 2007-10-30
• [Presentation] ADAM28 binds to and cleaves von Willebrand factor (2007)
  • Author(s): 望月 早月
  • Organizer: Gordon Research Conference on Matrix Metalloproteinase
  • Place of Presentation: II Ciocco Hotel and Resort Lucca (Bazga),Italy
  • Year and Date: 2007-06-07
• [Presentation] ADAM28 binds to and cleaves von Willebrand factor (2007)
  • Author(s): Satsuki Mochizuki, Kenji Soejima, Masayuki Shimoda and Yasunori Okada
  • Organizer: Gordon Research Conference on Matrix Metalloproteinase
  • Place of Presentation: Italy
  • Year and Date: 2007-06-06
• [Book] 分解の機構、MMP「エラスチンー構造・機能・病理」 (2008)
  • Author(s): 望月早月
  • Publisher: 日本エラスチン研究会
• [Book] エラスチン-構造・機能・病理 (2008)
  • Author(s): 望月 早月
  • Total Pages: 299
  • Publisher: エラスチン研究会
• [Book] TIMP-1, MMP-1, α2Mとは「日本医事新報」 (2007)
  • Author(s): 望月早月、岡田保典
  • Publisher: 日本医事新報社
• [Book] TIMP-1, MMP-1, α2Mとは (2007)
  • Author(s): 望月 早月
  • Total Pages: 134
  • Publisher: 日本医事新報社
• [Remarks] 慶應義塾大学COEプログラム「幹細胞医学と免疫学の基礎・臨床-体型拠点」での研究成果(下記URL)
• [Remarks]
  • URL: http://www.coe-stemcell.keio.ac.jp/jp/member/y_mochizuki.html
• [Remarks] 岡田研究室
• [Remarks]
  • URL: http://keio-okada-lab.jp/