Explorative research of novel factors for pancreatic cancer metastasis and proliferation based on analysis of cell dynamics

• Project/Area Number: 15K10201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: Yamauchi Akira 川崎医科大学, 医学部, 教授 (80372431)
• Co-Investigator(Kenkyū-buntansha): 栗林 太 川崎医科大学, 医学部, 教授 (60251443) ; 山村 真弘 川崎医科大学, 医学部, 講師 (70299204)
• Co-Investigator(Renkei-kenkyūsha): Nakamura Masafumi 九州大学, 医学部, 教授 (30372741)
• Research Collaborator: Sakaguchi Masakiyo 岡山大学, 大学院・医歯薬学総合研究科, 准教授 ; Katase Naoki 長崎大学, 大学院・医歯薬学総合研究科, 助教 ; Itadaini Masumi 川崎医科大学, 医学部, 実験補助員
• 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 転移惹起因子 / 走化性 / 遊走 / がん / 癌転移 / 膵癌 / 血清因子 / 脂質

Outline of Final Research Achievements

Pancreatic cancer is one of the diseases with poorest prognosis, which needs urgent countermeasures. Serum is known to be a strong chemoattractant, however, particular factors which cause cancer cell migration or metastasis remain unknown because of its heterogeneity. In this project, we explored the unknown factors which attract cancer cells, i.e. the metastasis promoting factors. At first, we established the evaluation system for cancer cell migration. Next, we found such factors in the non-protein, hydrophobic, and low-molecular-weight fraction. Also we found S100 proteins, known as factors produced in inflammation sites, as such factors. We are now evaluating these factors with animal model and with patients’ samples.

Research Products

• [Int'l Joint Research] University of Oxford/John Radcliffe Hospital/Weatherall Inst of Molecular Medicine(英国)
• [Int'l Joint Research] University of Oxford/John Radcliffe Hospital/Wheatherall Inst of Molecular Medicine(英国)
• [Journal Article] Monoclonal antibody 7D5 recognizes the R147 epitope on the gp91phox , phagocyte flavocytochrome b558 large subunit. (2018)
  • Author(s): Kawai C, Yamauchi A, Kuribayashi F.
  • Journal Title: Microbiology and Immunology Volume: 62 Issue: 4 Pages: 269-280
  • DOI: 10.1111/1348-0421.12584
  • Peer Reviewed
• [Journal Article] ｂ-1,3-galactosyl-O-glycosyl-glycoprotein ｂ-1,6-N-acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility. (2017)
  • Author(s): Sumardika I Wayan、Youyi Chen、Kondo Eisaku、Inoue Yusuke、Ruma I Made Winarsa、Murata Hitoshi、Kinoshita Rie、Yamamoto Ken-Ichi、Tomida Shuta、Shien Kazuhiko、Satoh Hiroki、Yamauchi Akira、Futami Junichiro、Putranto Endy Widya、Hibino Toshihiko、Toyooka Shinichi、Nishibori Masahiro、Sakaguchi Masakiyo
  • Journal Title: Oncology Reserch Volume: in press Issue: 3 Pages: 431-444
  • DOI: 10.3727/096504017x15031557924123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DKK3 Overexpression Increases Malignant Properties of Head and Neck Squamous Cell Carcinoma Cells. (2017)
  • Author(s): Katase N, Nishimatsu SI, Yamauchi A, Yamamura M, Terada K, Itadani M, Okada N, Hassan NMM, Nagatsuka H, Ikeda T, Nohno T, Fujita S.
  • Journal Title: Oncology Research Volume: 26(1) Issue: 1 Pages: 45-58
  • DOI: 10.3727/096504017x14926874596386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of pancreatic cancer cell migration with multiple parameters in vitro by using an optical real-time cell mobility assay device (2017)
  • Author(s): Yamauchi A, Yamamura M, Katase N, Itadani M, Okada N, Kobiki K, Nakamura M, Yamaguchi Y, Kuribayashi F.
  • Journal Title: BMC CancerMar Volume: 31 Issue: 1 Pages: 234-244
  • DOI: 10.1186/s12885-017-3218-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Homodimerisation of the Lymph Vessel Endothelial Receptor LYVE-1 through a Redox-Labile Disulfide is Critical for Hyaluronan Binding in Lymphatic Endothelium. (2016)
  • Author(s): Banerji S, Lawrance W, Metcalfe C, Briggs DC, Yamauchi A, Dushek O, van der Merwe PA, Day AJ, Jackson DG.
  • Journal Title: J Biol Chem Volume: 291(48) Issue: 48 Pages: 25004-25018
  • DOI: 10.1074/jbc.m116.736926
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells. (2016)
  • Author(s): Saho S, Satoh H, Kondo E, Inoue Y, Yamauchi A, Murata H, Kinoshita R, Yamamoto KI, Futami J, Putranto EW, Ruma IM, Sumardika IW, Youyi C, Suzawa K, Yamamoto H, Soh J, Tomida S, Sakaguchi Y, Saito K, Iioka H, Huh NH, Toyooka S, Sakaguchi M.
  • Journal Title: Cancer Microenviron. Volume: 9 Issue: 2-3 Pages: 93-105
  • DOI: 10.1007/s12307-016-0185-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-κB and ROS formation upon ligand binding. (2016)
  • Author(s): Ruma IM, Putranto EW, Kondo E, Murata H, Watanabe M, Huang P, Kinoshita R, Futami J, Inoue Y, Yamauchi A, Sumardika IW, Youyi C, Yamamoto K, Nasu Y, Nishibori M, Hibino T, Sakaguchi M.
  • Journal Title: Clin Exp Metastasis Volume: 33 Issue: 6 Pages: 609-627
  • DOI: 10.1007/s10585-016-9801-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The Effect of ROS on the chemotaxis of Inflammatory cells (2017)
  • Author(s): Yamauchi A, Okamoto S, Itadani M, Kawai C, Kuribayashi F.
  • Organizer: Con Bio 2017第41回日本分子生物学会年会・第91回日本生化学会大会合同大会
• [Presentation] ROS suppress the cellular chemotaxis (2017)
  • Author(s): Yamauchi A, Okamoto S, Kuribayashi F.
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society, ICIS 2017
  • Int'l Joint Research
• [Presentation] がん微小環境における酸化還元状態のリンパ行性転移への影響 (2017)
  • Author(s): 山内 明、山村 真弘、片瀬 直樹、栗林 太
  • Organizer: 第8回川崎医科大学学術集会
• [Presentation] Heat shock protein 90 inhibitors suppress PDGFRA reactivation and other receptor tyrosine kinase activation important in drug resistant gastrointestinal stromal tumors. (2017)
  • Author(s): Yamamura M,Yamauchi A, Katase N, Okawaki M, Katata Y, Kuribayashi F, Kurebayashi J, Yamaguchi Y.
  • Organizer: American Association for Cancer Research Annual Meeting 2017
  • Int'l Joint Research
• [Presentation] Gemcitabineは膵癌細胞の走化性に影響を与えないがDasatinibは走化性を抑制する (2016)
  • Author(s): 山内 明, 山村 真弘, 片瀬直樹, 板谷益美, 山口佳之, 栗林 太
  • Organizer: 第54回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-10-20
• [Presentation] 癌転移を惹起・増強する血清因子の探索 (2016)
  • Author(s): 山内 明, 山村 真弘, 片瀬直樹, 山口佳之
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-10-06
• [Presentation] 肝細胞癌標的治療薬としてのDPP-4阻害剤の分子生物学的解析 (2016)
  • Author(s): 仁科惣治, 山内 明, 佐々木恭, 小山展子, 富山恭行, 吉岡奈穂子, 原 裕一, 日野啓輔
  • Organizer: 第12回広島肝臓研究センターシンポジウム
  • Place of Presentation: ホテルグランヴィア広島（広島）
  • Year and Date: 2016-06-25
• [Presentation] HSP90 inhibitor inhibit the activation of multiple kinase pathways and migration of pancreatic cancer cells. (2016)
  • Author(s): Masahiro Yamamura, Akira Yamauchi, Naoki Katase, Yosuke Katata, Makoto Okawaki, Akira Sawaki, Tsutomu Nohno, Yoshiyuki Yamaguchi
  • Organizer: American Association for Cancer Research, Precision Medicine Series: TARGETING THE VULNERABILITIES OF CANCER
  • Place of Presentation: JW Marriott Marquis Miami (Miami, Florida, USA)
  • Year and Date: 2016-05-18
  • Int'l Joint Research
• [Presentation] 肝細胞癌進展のバイオマーカーならびに治療標的としてのCD26（DPP4）の意義 (2016)
  • Author(s): 仁科 惣治, 山内 明, 日野啓輔
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2016-04-23
• [Presentation] 肝細胞癌治療標的としてのCD26(DPP4) の意義 (2016)
  • Author(s): 仁科惣治, 山内明, 小山展子, 富山恭行, 吉岡奈穂子, 原裕一, 日野啓輔
  • Organizer: 第１１３回日本内科学会総会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2016-04-16
• [Presentation] 口腔癌由来細胞におけるDKK3遺伝子発現の影響 (2015)
  • Author(s): 片瀬 直樹、寺田 久美子、西松 伸一郎、鈴木 貴弘、松﨑 秀紀、山村 真弘、山内 明、大槻 剛巳、濃野 勉
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（神戸）
  • Year and Date: 2015-12-01
• [Presentation] 肝細胞癌治療標的としてのCD26（DPP-4）の分子生物学的解析 (2015)
  • Author(s): 仁科惣治, 山内明, 小山展子, 富山恭行, 吉岡奈穂子, 原裕一, 日野啓輔
  • Organizer: 第41回日本肝臓学会西部会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [Presentation] CD26 (DPP-4) as a molecular target for HCC treatment (2015)
  • Author(s): S. Nishina, A. Yamauchi, K. Hino
  • Organizer: Japan Digestive Disease Week 2015
  • Place of Presentation: グランドプリンスホテル新高輪(東京)
  • Year and Date: 2015-10-08
• [Presentation] HSP90 inhibitor inhibit the activation of multiple kinase pathways of pancreatic cancer cells (2015)
  • Author(s): Masahiro Yamamura, Akira Yamauchi, Naoki Katase,Toshihiro Hirai
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [Presentation] Functional analyses of DKK3 in oral squamous cell carcinoma cell lines (2015)
  • Author(s): Naoki Katase, Masahiro Yamamura, Akira Yamauchi, Takahiro Suzuki, Kumiko Terada, Shin-ichiro Nishimatsu, Tsutomu Nohno
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [Presentation] Suppressing pancreatic cancer metastasis by small molecular compunds (2015)
  • Author(s): Yamauchi A, Yamamura M, Katase N, Itadani M, Okada N, Yamaguchi Y, Nohno T, Kuribayashi F
  • Organizer: International Conference of Cancer Immunotherapy and Macrophages 2015
  • Place of Presentation: University of Tokyo (Tokyo)
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [Presentation] 肝細胞癌標的治療薬としてのDPP-4阻害剤の分子生物学的解析 (2015)
  • Author(s): 仁科惣治, 山内明, 小山展子, 富山恭行, 吉岡奈穂子, 原裕一, 日野啓輔
  • Organizer: 第11回広島肝臓プロジェクト研究センターシンポジウム
  • Place of Presentation: ホテルグランヴィア広島(広島)
  • Year and Date: 2015-07-04
• [Presentation] The new molecular target therapy of Hsp90 inhibition in esophageal squamous cell carcinoma (2015)
  • Author(s): Masahiro Yamamura, Tsutomu Nohno, Akira Yamauchi, Naoki Katase, Makoto Okawaki, Akira Sawaki, Hideo Matsumoto, Toshihiro Hirai, Yoshiyuki Yamaguchi
  • Organizer: AACR Annual Meeting 2015
  • Place of Presentation: Pennsylvania Convention Center（Philadelphia, USA）
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Remarks] 川崎医科大学 教員情報 山内 明
  • URL: https://kwweb-res.kawasaki-m.ac.jp/kwmhp/KgApp?section=13&kyoinId=Kgyyggyg
• [Remarks] 川崎医科大学 教員情報
  • URL: http://kwweb-res.kawasaki-m.ac.jp/kwmhp/KgApp?section=13&kyoinId=Kgyyggyg
• [Patent(Industrial Property Rights)] 新規抗腫瘍剤 (2018)
  • Inventor(s): 山内明、町支臣成
  • Industrial Property Rights Holder: 学校法人川崎学園、学校法人福山大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-059074
  • Filing Date: 2018