Analysis for the effect of C5a receptor on cancer cell and development for targeted therapeutic strategy to C5a receptor

• Project/Area Number: 25462099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: NITTA Hidetoshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90555749)
• Co-Investigator(Kenkyū-buntansha): BABA Hideo 熊本大学, 大学院生命科学研究部, 教授 (20240905) ; NAKAHARA Osamu 熊本大学, 医学部附属病院, 非常勤診療医師 (40583042) ; BEPPU Toru 熊本大学, 医学部附属病院, 特任教授 (70301372) ; TAKAMAORI Hiroshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90363514)
• Research Collaborator: KAIDA Takayoshi 熊本大学, 大学院生命科学研究部, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 補体C5a / C5a受容体 / 胃癌浸潤・転移 / 胃癌 / 補体 / 浸潤 / 肝転移 / C5aR / 浸潤、転移

Outline of Final Research Achievements

We examined the effect of C5a receptor (C5aR) on Gastric cancer (GC). Two human GC cell lines had high C5aR expression. An invasion assay revealed that C5a stimulation promoted the invasive ability of them. Moreover, overexpression of C5aR in GC cells enhanced the conversion of RhoA-GDP to RhoA-GTP after C5a stimulation and caused morphological changes, including increased expression of stress fibers and filopodia. Examination of tumor specimens from patients with GC revealed that high C5aR expression was associated with increased invasion depth, vascular invasion and advanced stage. The 5-year overall survival of patients with high C5aR expression was significantly worse than that of patients with low expression. This study is the first to demonstrate that C5aR promotes GC cell invasion by activating RhoA and is associated with a poor prognosis in GC patients. Therefore, this study provides a biomarker for GC patients who require an advanced therapeutic strategy.

Research Products

• [Journal Article] Chemotherapy-induced Nausea and Vomiting in Patients with Hepatobiliary and Pancreatic Cancer Treated with Chemotherapy: A Prospective Observational Study by the CINV Study Group of Japan (2016)
  • Author(s): Hidetoshi Nitta, Hideo Baba, Kazuya Sugimori, Junji Furuse, Shinichi Ohkawa, Kazuhide Yamamoto, Hironobu Minami, Mototsugu Shimokawa, Go Wakabayashi and Keisuke Aiba
  • Journal Title: Anticancer Research Volume: 36(4) Pages: 1929-1936
  • Peer Reviewed
• [Journal Article] Enhancement of human cancer cell motility and invasiveness by anaphylatoxin C5a via aberrantly expressed C5a-receptor (CD88). (2013)
  • Author(s): Nitta, H. et al.
  • Journal Title: Clinical Cancer Reseach Volume: 19 Issue: 8 Pages: 2004-2013
  • DOI: 10.1158/1078-0432.ccr-12-1204
  • Peer Reviewed
• [Journal Article] Prognosis assessment of patients with refractory ascites treated with a peritoneovenous shunt. (2013)
  • Author(s): Nitta H, Okamura S, Mizumoto T, Matsushita H, Nishimura T, Shimokawa Y, Kimura M, Baba H.
  • Journal Title: Hepatogastroenterology Volume: 60 Pages: 1607-1610
  • Peer Reviewed
• [Journal Article] Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion. (2013)
  • Author(s): Nitta H, Beppu T, Imai K, Hayashi H, Chikamoto A, Baba H.
  • Journal Title: Would Journal of Surgery Volume: 37 Issue: 5 Pages: 1034-1042
  • DOI: 10.1007/s00268-013-1957-1
  • Peer Reviewed
• [Journal Article] Effects of the closing speed of stapler jaws on bovine pancreases. (2013)
  • Author(s): Chikamoto A, Hashimoto D, Ikuta Y, Tsuji A, Abe S, Hayashi H, Imai K, Nitta H, Ishiko T, Watanabe M, Beppu T, Baba H.
  • Journal Title: Surgical endoscopyy Volume: 28(1) Issue: 1 Pages: 336-340
  • DOI: 10.1007/s00464-013-3157-3
  • URL: http://link.springer.com/article/10.1007%2Fs00534-012-0587-6
  • Peer Reviewed
• [Journal Article] Enhancer of Zeste Homolog 2 (EZH2) Promotes Progression of Cholangiocarcinoma Cells by Regulating Cell Cycle and Apoptosis. (2013)
  • Author(s): Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H.
  • Journal Title: Ann Surg Oncol Volume: 3 Issue: S3 Pages: 667-675
  • DOI: 10.1245/s10434-013-3135-y
  • Peer Reviewed
• [Presentation] 補体C5aを介した胃癌浸潤能の亢進 (2015)
  • Author(s): 甲斐田剛圭、新田英利、北野雄希、山村謙介、有馬浩太、東孝暁、髙城克暢、林洋光、橋本大輔、近本亮、石河隆敏、別府透、馬場秀夫
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-10-08
• [Presentation] 胃癌におけるC5a受容体高発現の予後因子としての意義 (2015)
  • Author(s): 甲斐田剛圭、新田英利、東孝暁、髙城克暢、岡部弘尚、林洋光、橋本大輔、別府透、馬場秀夫、近本亮
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: アクトシティ浜松（鳥取県）
  • Year and Date: 2015-07-16
• [Presentation] Relation between expression of C5a receptor and clinicopathological factors in patients with gastric cancer (2015)
  • Author(s): Takayoshi Kaida, Hidetoshi Nitta, Kota Arima, Hideaki Takeyama, Takaaki Higashi, Katunobu Taki, Hiromitsu Hayashi, Akira Chikamoto, Toru Beppu and Hideo Baba
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Pennsylvania Convention Center（米国・フィラデルフィア）
  • Year and Date: 2015-04-21
  • Int'l Joint Research
• [Presentation] Enhancement of human cancer cell migration and invasion by anaphylatoxin C5a via aberrantly expressed C5a-receptor (2013)
  • Author(s): 新田 英利
  • Organizer: Federation of Asian Clinical Oncology
  • Place of Presentation: 厦門（中国）