Analysis of tumor-stromal interaction via complement C5a receptor in cancer microenvironment

• Project/Area Number: 15K10171
• 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: NAKAHARA Osamu 熊本大学, 医学部附属病院, 非常勤診療医師 (40583042)
• Co-Investigator(Kenkyū-buntansha): 岡部 弘尚 熊本大学, 医学部附属病院, 助教 (40573621) ; 橋本 大輔 熊本大学, 医学部附属病院, その他 (80508507) ; 新田 英利 熊本大学, 医学部附属病院, 助教 (90555749)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: C5a受容体 / ヒト肝星細胞 / 肝細胞癌 / 補体C5a / 癌間質細胞 / 肝星細胞 / 浸潤 / 転移

Outline of Final Research Achievements

The Aim of this study is to analyze tumor-stromal interaction via C5a-C5aR axis in hepatocellular carcinoma (HCC).
At first, we investigated whether human hepatic stellate cells (HSC) were in activated state or not in resected HCC specimen using confocal microscope. The result that αSMA staining, which is marker of activation in HSC, was detected in HSC around HCC lesions, meant that HSC was in activated state around human HCCs. In vitro, western blotting analysis revealed C5aR expression at HSC in a time dependent manner. Moreover, HSC increased αSMA expression by C5a stimulation. Therefore, HSC could be activated by C5a-C5aR axis. In addition, C5a stimulation increased HCC invasion and that was inhibited by C5aR-antagonist. From these results, C5a-C5aR could be a target therapy for HCC treatment.

Research Products

• [Journal Article] Clinical significance of half-lives of tumor markers α-fetoprotein and des-γ-carboxy prothrombin after hepatectomy for hepatocellular carcinoma. (2018)
  • Author(s): Tsukamoto M, Nitta H, Imai K, Higashi T, Nakagawa S, Okabe H, Arima K, Kaida T, Taki K, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H
  • Journal Title: Hepatol Res. Volume: 48 Issue: 3
  • DOI: 10.1111/hepr.12942
  • Peer Reviewed
• [Journal Article] Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma. (2017)
  • Author(s): itta H, Nakagawa S, Kaida T, Arima K, Higashi T, Taki K, Okabe H, Hayashi H, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H.
  • Journal Title: Surg Today Volume: 47(3) Issue: 3 Pages: 375-384
  • DOI: 10.1007/s00595-016-1385-6
  • Peer Reviewed
• [Journal Article] Preoperative platelet-to-lymphocyte ratio can predict recurrence beyond the Milan criteria after hepatectomy for patients with hepatocellular carcinoma. (2016)
  • Author(s): Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Higashi T, Taki K, Nakagawa S, Okabe H, Hayashi H, Imai K, Hashimoto D, Yamashita YI, Chikamoto A, Ishiko T, Beppu T, Baba H.
  • Journal Title: Hepatol Res Volume: Epub ahead of print Issue: 10 Pages: 991-999
  • DOI: 10.1111/hepr.12835
  • Peer Reviewed
• [Journal Article] C5a receptor (CD88) promotes motility and invasiveness of gastric cancer by activating RhoA. (2016)
  • Author(s): Kaida T, Nitta H, Kitano Y, Yamamura K, Arima K, Izumi D, Higashi T, Kurashige J, Imai K, Hayashi H, Iwatsuki M, Ishimoto T, Hashimoto D, Yamashita Y, Chikamoto A, Imanura T, Ishiko T, Beppu T, Baba H.
  • Journal Title: Oncotarget. Volume: 20(7) Issue: 51 Pages: 84798-84809
  • DOI: 10.18632/oncotarget.12656
  • Peer Reviewed
• [Journal Article] Degenerative hepatic hemangioma mimicking biliary cystadenocarcinoma. (2016)
  • Author(s): Kaida T, Higashi T, Kitano Y, Yamamura K, Arima K, Taki K, Imai K, Nitta H, Hashimoto D, Chikamoto A, Namimoto T, Nakahara O, Beppu T, Baba H
  • Journal Title: J Gastroenterol Hepatol Volume: 31(8) Issue: 8 Pages: 1385-1385
  • DOI: 10.1111/jgh.13325
  • Peer Reviewed
• [Journal Article] Expression of anaphylatoxin C5a receptor in gastric cancer: Implications with vascular invasion and patient outcome. (2016)
  • Author(s): Nitta, H., Shimose, T., Emi, Y., Imamura, T., Ohnishi, K., Kusumoto, T., Yamamoto. M., Fukuzawa, K., Takahashi, I., Higashi, H., Tsuji, A., Akagi, Y., Oki, E., Maehara, Y., & Baba, H.
  • Journal Title: Med. Oncol. Volume: 33 Issue: 11 Pages: 118-118
  • DOI: 10.1007/s12032-016-0834-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chemotherapy-induced Nausea and Vomiting in Patients with Hepatobiliary and Pancreatic Cancer Treated with Chemotherapy (2016)
  • Author(s): Nitta H, Baba H, Sugimori K, Furuse J, Ohkawa S, Yamamoto K, Minami H, Shimokawa M, Wakabayashi GO, Aiba K, Japan CSGo
  • Journal Title: Anticancer Res Volume: 36(4) Pages: 1929-35
  • Peer Reviewed
• [Journal Article] Chemotherapy-induced nausea and vomiting in hepatobiliary and pancreatic cancer patients 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, CINV Study Group of Japan.
  • Journal Title: Anticancer Res. Volume: 36(4) Pages: 1929-35
  • Peer Reviewed
• [Presentation] Prognostic value and prediction of extra-tumoral microvascular invasion among candidates for hepatectomy or liver transplantation for HCC (2017)
  • Author(s): Hidetoshi Nitta, Marc-Antoine Allard, Gabriella Pittau, Oriana Ciacio, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Hideo Baba, and Rene Adam
  • Organizer: EASL2017
  • Int'l Joint Research
• [Presentation] Predictive model for microvascular invasion of hepatocellular carcinoma among candidates for either hepatectomy or liver transplantation. (2017)
  • Author(s): Hidetoshi Nitta, Marc-Antoine Allard, Mylène Sebagh, Gabriella Pittau, Oriana Ciacio, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Catherine Guettier, Didier Samuel, Hideo Baba, and Rene Adam
  • Organizer: ASCO2017
  • Int'l Joint Research
• [Presentation] Analysis of risk factors of early recurrence and ideal surgical margin for hepatocellular carcinoma. (2017)
  • Author(s): Hidetoshi Nitta, Marc-Antoine Allard, Mylene Sebagh, Oriana Ciacio, Gabriella Pittau, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Hideo Baba, and Rene Adam
  • Organizer: ESMO GI 2017
  • Int'l Joint Research
• [Presentation] Establishment of predictive model for microvascular invasion of hepatocellular carcinoma and Clinical usage of the model for decision of surgical strategy. (2017)
  • Author(s): Hidetoshi Nitta, Marc-Antoine Allard, Mylene Sebagh, Gabriella Pittau, Oriana Ciacio1, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Catherine Guettier, Didier Samuel, Hideo Baba, and Rene Adam
  • Organizer: ILTS2017
  • Int'l Joint Research
• [Presentation] Prognostic value and prediction of extra-tumoral microvascular invasion among patients who candidate for hepatectomy or liver transplantation for hepatocellular carcinoma. (2017)
  • Author(s): Hidetoshi Nitta , Marc-Antoine Allard, Gabriella Pittau, Oriana Ciacio, Eric Vibert, Antonio Sa Cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Hideo Baba, Rene Adam
  • Organizer: EASL2017
  • Place of Presentation: Amsterdam, Netherlands
  • Int'l Joint Research
• [Presentation] 肝切除におけるソフト凝固システム、バイポーラ凝固切開装置、自動縫合器の有用性と問題点 (2015)
  • Author(s): 新田英利、坂本悠樹、山下晃平、大徳暢哉、武山秀晶、甲斐田剛圭、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27回日本肝胆膵外科学会・学術集会
  • Place of Presentation: ホテルグランパシフィック LE DAIBA（東京）
  • Year and Date: 2015-06-11