Investigation and therapeutic application of the cancerauto-activation pathway through generation of anaphylatoxin C5a
Project/Area Number |
22590363
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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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)
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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)
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Project Period (FY) |
2010 – 2012
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Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | C5a / 癌 / 浸潤 / 増殖 / 転移 / プロテアーゼ / 阻害剤 / 受容体拮抗剤 / フューリン / 自己活性化 / 産生 / MMP / 運動性 / CD88 / 受容体 / 血栓症 |
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.
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Report
(4 results)
Research Products
(43 results)
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[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
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Journal Title
J. Med. Case Report
Volume: 6
Pages: 378-378
Related Report
Peer Reviewed
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[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
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Journal Title
FEBSLett
Volume: 586
Pages: 3613-3617
Related Report
Peer Reviewed
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[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
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Journal Title
Biol. Chem
Volume: 393
Pages: 1193-1200
Related Report
Peer Reviewed
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[Journal Article] Severe bleeding tendency caused by a rare complication of excessive fibrinolysis with disseminated intravascular coagulation in a 51-year-old Japanese man with prostate cancer:a case report.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.
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Journal Title
Journal of Medical Case Reports
Volume: 6
Issue: 1
Pages: 378-378
DOI
Related Report
Peer Reviewed
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[Journal Article] 進行性腎盂尿管癌の臨床において手術に役立つ腎盂尿管の解剖(Gerota筋膜)2012
Author(s)
和田孝浩, 今村隆寿, 高橋渡, 河野吉昭, 本多次朗, 田上憲一郎, 仲西寿朗, 谷川史城, 前田喜寛, 中村圭輔, 江藤正俊, 桑原朋広
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Journal Title
泌尿器外科
Volume: 25
Pages: 667-672
Related Report
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[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
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Journal Title
Microbiology
Volume: 157
Pages: 786-792
Related Report
Peer Reviewed
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[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
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Journal Title
Clin.Cancer Res
Volume: (in press)
Related Report
Peer Reviewed
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[Presentation] Abberant expression C5aR in metastatic renal cell carcinoma.2012
Author(s)
Maeda, Y., Wada Y., Kawano, Y., Kikuchi, K., Takahashi, W., Honda, J., Nakanishi, J., Imamura, T., & Eto, M.
Organizer
107th American Urological Association (AUA) Annual Meeting
Place of Presentation
Georgia World Congress Center, Atlanta, USA.
Related Report
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[Presentation] Aberrant expression of C5aR in metastatic renal cell carcinoma.2012
Author(s)
Maeda, Y.,, Wada, Y., Kawano, Y., Kikuchi, K., Takahashi, W., Honda, J., Nakanishi, J., Yatsuda, J., Murakami, Y., Imamura, T., & Eto, M.
Organizer
The 29th Japan-Korea Urological Congress
Place of Presentation
鹿児島市:城山観光ホテル
Related Report
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[Presentation] Frequent Expression of C5aR in Metastatic Renal Cell Carcinoma.2012
Author(s)
Maeda, Y.,, Wada, Y., Kawano, Y., Kikuchi, K., Takahashi, W., Honda, J., Nakanishi, J., Yatsuda, J., Murakami, Y., Imamura, T., & Eto, M.
Organizer
32nd SIU Congress 2012
Place of Presentation
福岡市:福岡国際会議場
Related Report
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[Presentation] Anaphylatoxin C5a enhances human cancer cell motility and invasiveness via aberrantly expressed C5a-receptor (CD88).2012
Author(s)
Imamura, T., Murakami, Y., Wada, Y., Kawano, Y., & Nitta, H.
Organizer
2012 Annual Meeting of The American Society for Cell Biology
Place of Presentation
The Moscone Center, San Francisco, USA
Related Report
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[Presentation] Urine of AKI patients promotes metanephrotic cell growth and recovery of renal function after ischemic-reperfusion injury in mouse.2012
Author(s)
Kitamoto, Y., Kitamura, H., Sugai, H., Taguma, Y., Imamura, T., & Yorinaga, H.
Organizer
2012 Annual Meeting of The American Society for Cell Biology
Place of Presentation
The Moscone Center, San Francisco, USA
Related Report
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