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2012 Fiscal Year Final Research Report

Investigation and therapeutic application of the cancerauto-activation pathway through generation of anaphylatoxin C5a

Research Project

  • PDF
Project/Area Number 22590363
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

IMAMURA Takahisa  熊本大学, 大学院・生命科学研究部, 准教授 (20176499)

Co-Investigator(Renkei-kenkyūsha) NISHINO Norikazu  九州工業大学, 生命体工学研究科, 教授 (40145165)
IRIE Atsushi  熊本大学, 生命科学研究部, 准教授 (30250343)
Project Period (FY) 2010 – 2012
KeywordsC5a / 癌 / 浸潤 / 増殖 / 転移 / プロテアーゼ / 阻害剤 / 受容体拮抗剤
Research Abstract

Anaphylatoxin C5a receptor (C5aR) was expressed in cancer cellsfrom all organs examined and at various rates in organs. Several cancer cell lines alsoexpressed C5aR. C5a augmented C5aR-expressing cancer cell invasion in a MMP-6 dependentmanner in Matrigel chambers and in implanted nude mouse skin. C5a also enhanced cancercell lung metastasis in a C5aR-dependent manner. By cell membrane-bound furin-like serineprotease cancer cells generated C5a from C5, even it in plasma, augmenting theirinvasiveness. These C5a effects on cancer cells were inhibited by antibodies againsteither C5a or C5aR, and by a C5aR antagonist. These results indicate presence of a cancercell autoactivation pathway via C5a generation and suggest availability of a new cancertherapy targeting the C5a-C5aR axis or the cancer protease.

  • Research Products

    (8 results)

All 2012 2011 2010 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Severe bleeding tendencycaused by excessive fibrinolysis withdisseminated intravascular coagulationin a prostate cancer patient: a casereport2012

    • Author(s)
      Wada, Y., Uchiba, M., Kawano, Y., Kai,N., Takahashi, W., Honda, J., Tanoue, K.,Maeda, Y., Murakami, Y., Eto, M., &Imamura, T
    • Journal Title

      J. Med. Case Report

      Volume: 6 Pages: 378

    • Peer Reviewed
  • [Journal Article] The tail nick augmentsAeromonas sobria serine protease (ASP)activity in plasma through retarding_2-macroglobulin2012

    • Author(s)
      Murakami, Y., Wada, Y., Kobayashi, H.,Hasegawa, M., Okamoto, K., Eto, M., &Imamura, T
    • Journal Title

      FEBSLett

      Volume: 586 Pages: 3613-3617

    • Peer Reviewed
  • [Journal Article] Inhibition of Aeromonas sobria serine2-macroglobulin2012

    • Author(s)
      Murakami, Y., Wada, Y., Kobayashi, H.,Irie, A., Hasegawa, M., Yamanaka, H.,Okamoto, K., Eto, M., & Imamura, T
    • Journal Title

      Biol. Chem

      Volume: 393 Pages: 1193-1200

    • Peer Reviewed
  • [Journal Article] Degradation of fibrinogen and collagenby staphopains, cysteine proteasesreleased from Staphylococcus aureus2011

    • Author(s)
      Ohbayashi, T., Irie, A., Murakami, Y.,Nowak, M., Potempa, J., Nishimura, Y.,Shinohara, M., & Imamura, T
    • Journal Title

      Microbiology

      Volume: 157 Pages: 786-792

    • Peer Reviewed
  • [Journal Article] Enhancement of human cancer cellmotility and invasiveness byanaphylatoxin C5a via aberrantlyexpressed C5a-receptor (CD88)

    • Author(s)
      Nitta, H., Wada, Y., Kawano, Y.,Murakami, Y., Irie, A., Taniguchi, K.,Kikuchi, K., Yamada, G., Suzuki, K.,Honda, J., Wilson-Morifuji, M., Araki,N., Eto, M., Baba, H., & Imamura, T
    • Journal Title

      Clin.Cancer Res

      Volume: (in press)

    • Peer Reviewed
  • [Book] Proteasesand their receptors in inflammation2011

    • Author(s)
      Imamura, T., & Potempa, J
    • Total Pages
      275-290
    • Publisher
      Microbial protases: Relevance to theinflammatory response
  • [Book] 救急・集中治療2010

    • Author(s)
      今村隆寿、丸藤哲
    • Total Pages
      1140-1144
  • [Remarks]

    • URL

      http://www.kumamoto-u.ac.jp/seeds/seeds/61580016/index.html

URL: 

Published: 2014-08-29  

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