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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kumamoto 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
• Keywords: C5a / 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

• [Journal Article] Severe bleeding tendencycaused by excessive fibrinolysis withdisseminated intravascular coagulationin a prostate cancer patient: a casereport (2012)
  • 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-macroglobulin (2012)
  • 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-macroglobulin (2012)
  • 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 aureus (2011)
  • 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 inflammation (2011)
  • 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