肝癌幹細胞におけるｍｉＲＮＡの解析：発癌予防と抑制そして転移制圧に向けて

2013 Fiscal Year Annual Research Report

• Project/Area Number: 24890081
• Research Institution: Gifu University
• Principal Investigator: 末次 淳 岐阜大学, 医学部附属病院, 助教 (30340079)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: 肝癌 / 癌幹細胞 / miRNA

Research Abstract

癌は、原発巣及び転移巣において微小環境を形成し、その癌組織内は癌細胞のみでなく、周囲の癌関連細胞が重要な役割を果たしている。癌細胞の肝転移において、蛍光蛋白を用いてそれら癌微小環境を形成する細胞をシングルレベルで画像化し、癌細胞周囲の癌関連細胞特に癌関連繊維芽細胞（cancer associated fibroblasts）や腫瘍関連マクロフャージ（tumor associated macrophages）の重要性が明らかにされた。実際、転移の際にエクソソームが転移巣を形成するときに、転移前に特に繊維芽細胞内に入り込み、転移する環境を形成することを視覚的に証明した。さらに、これらが血液などの体液中に分泌され、他の細胞に取り込まれることを確かめられ、エクソソームを介した細胞間コミュニケーションが存在することを示唆していた。癌形成及び転移時において、癌細胞と周囲の細胞間のコミュニケーションは必要であることが証明された。

Current Status of Research Progress

Reason

25年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

25年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Pharmaceutical and nutraceutical approaches for preventing liver carcinogenesis: chemoprevention of hepatocellular carcinoma using acyclic retinoid and branched-chain amino acids. (2014)
  • Author(s): Shimizu M, Shirakami Y, Hanai T, Imai K, Suetsugu A, Takai K, Shiraki M, Moriwaki H.
  • Journal Title: Mol Nutr Food Res. Volume: 58 Pages: 124-135
  • DOI: 10.1002/mnfr.201300538.
  • Peer Reviewed
• [Journal Article] Efficacy of Salmonella typhimurium A1-R Versus Chemotherapy on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX). (2014)
  • Author(s): Hiroshima Y, Zhao M, Maawy A, Zhang Y, Katz MH, Fleming JB, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Cell Biochem. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1002/jcb.24769.
  • Peer Reviewed
• [Journal Article] Imaging the efficacy of UVC irradiation on superficial brain tumors and metastasis in live mice at the subcellular level. (2013)
  • Author(s): Momiyama M, Suetsugu A, Kimura H, Kishimoto H, Aki R, Yamada A, Sakurada H, Chishima T, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Cell Biochem. Volume: 114 Pages: 428-434
  • DOI: 10.1002/jcb.24381.
  • Peer Reviewed
• [Journal Article] Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude mouse models. (2013)
  • Author(s): Suetsugu A, Honma K, Saji S, Moriwaki H, Ochiya T, Hoffman RM.
  • Journal Title: Adv Drug Deliv Rev. Volume: 65 Pages: 383-390
  • DOI: 10.1016/j.addr.2012.08.007.
  • Peer Reviewed
• [Journal Article] Subcellular real-time imaging of the efficacy of temozolomide on cancer cells in the brain of live mice. (2013)
  • Author(s): Momiyama M, Suetsugu A, Chishima T, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 103-106
  • Peer Reviewed
• [Journal Article] Enhanced resection of orthotopic red-fluorescent-protein-expressing human glioma by fluorescence-guided surgery in nude mice. (2013)
  • Author(s): Momiyama M, Hiroshima Y, Suetsugu A, Tome Y, Mii S, Yano S, Bouvet M, Chishima T, Endo I, Hoffman RM.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 107-111
  • Peer Reviewed
• [Journal Article] Liver acid sphingomyelinase inhibits growth of metastatic colon cancer. (2013)
  • Author(s): Osawa Y, Suetsugu A, Matsushima-Nishiwaki R, Yasuda I, Saibara T, Moriwaki H, Seishima M, Kozawa O.
  • Journal Title: J Clin Invest. Volume: 123 Pages: 834-843
  • DOI: 10.1172/JCI65188.
  • Peer Reviewed
• [Journal Article] Dynamic subcellular imaging of cancer cell mitosis in the brain of live mice. (2013)
  • Author(s): Momiyama M, Suetsugu A, Kimura H, Chishima T, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 1367-1371
  • Peer Reviewed
• [Journal Article] Free fatty acid as a marker of energy malnutrition in liver cirrhosis. (2013)
  • Author(s): Hanai T, Shiraki M, Nishimura K, Imai K, Suetsugu A, Takai K, Shimizu M, Naiki T, Moriwaki H.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 218-228
  • DOI: 10.1111/hepr.12112.
  • Peer Reviewed
• [Journal Article] In vivo fluorescence imaging reveals the promotion of mammary tumorigenesis by mesenchymal stromal cells. (2013)
  • Author(s): Ke CC, Liu RS, Suetsugu A, Kimura H, Ho JH, Lee OK, Hoffman RM.
  • Journal Title: PLoS One. Volume: 8 Pages: e69658
  • DOI: 10.1371/journal.pone.0069658.
  • Peer Reviewed
• [Journal Article] Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. (2013)
  • Author(s): Hiroshima Y, Zhao M, Zhang Y, Maawy A, Hassanein MK, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Cell Cycle. Volume: 12 Pages: 2774-2780
  • DOI: 10.4161/cc.25872.
  • Peer Reviewed
• [Journal Article] Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. (2013)
  • Author(s): He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M.
  • Journal Title: Cell. Volume: 155 Pages: 384-396
  • DOI: 10.1016/j.cell.2013.09.031.
  • Peer Reviewed
• [Journal Article] Imaging nuclear - cytoplasm dynamics of cancer cells in the intravascular niche of live mice. (2013)
  • Author(s): Suetsugu A, Jiang P, Moriwaki H, Saji S, Bouvet M, Hoffman RM.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 4229-4236
  • Peer Reviewed
• [Journal Article] Development of a clinically-precise mouse model of rectal cancer. (2013)
  • Author(s): Kishimoto H, Momiyama M, Aki R, Kimura H, Suetsugu A, Bouvet M, Fujiwara T, Hoffman RM.
  • Journal Title: PLoS One. Volume: 8 Pages: e79453
  • DOI: 10.1371/journal.pone.0079453.
  • Peer Reviewed
• [Presentation] シンポジウム C型慢性肝炎IFN治療SVR後の発癌症例の検討 (2013)
  • Author(s): 末次 淳、内木隆文、森脇久隆
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜
  • Year and Date: 20131206-20131207
• [Presentation] Salmonella typhimurium A1-R targets chemoresistant stem-like human pancreatic cancer cells. (2013)
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: American Society of Clinical Oncology (ASCO)
  • Place of Presentation: Chicago, （アメリカ）
  • Year and Date: 20130531-20130604
• [Presentation] Salmonella typhimurium A1-R effectively targets human-patient pancreatic tumorgrafts in nude mice. (2013)
  • Author(s): Ming Zhao, Matthew H. G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman, Yukihiko Hiroshima
  • Organizer: American Society of Clinical Oncology (ASCO)
  • Place of Presentation: Chicago, （アメリカ）
  • Year and Date: 20130531-20130604
• [Presentation] CHARACTERIZATION AND IMAGING OF CD133+ LIVER CANCER STEM CELLS (2013)
  • Author(s): A. Suetsugu, Y. Osawa, H. Aoki, T. Kunisada, H. Tsurumi,R.M. Hoffman, H. Moriwaki
  • Organizer: European Association for the Study of the Liver (EASL)
  • Place of Presentation: Amsterdam, （オランダ）
  • Year and Date: 20130424-20130428
• [Presentation] ACID SPHINGOMYELINASE INHIBITS GROWTH OF METASTATIC LIVER TUMOR (2013)
  • Author(s): Y. Osawa, A. Suetsugu, H. Moriwaki, O. Kozawa
  • Organizer: European Association for the Study of the Liver (EASL)
  • Place of Presentation: Amsterdam, （オランダ）
  • Year and Date: 20130424-20130428
• [Presentation] Efficacy of Salmonella typhimurium A1-R on chemoresistant stem-like human pancreatic cancer cells (2013)
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman.
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: Washington DC, （アメリカ）
  • Year and Date: 20130406-20130410
• [Presentation] Cancer cell location in tumor determines cell cycle position and dormancy (2013)
  • Author(s): Shuya Yano, Yasunori Tome, Michelle Digman, Masashi Momiyama, Atsushi Suetsugu, Enrico Gratton, Robert M. Hoffman.
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: Washington DC, （アメリカ）
  • Year and Date: 20130406-20130410
• [Presentation] Imaging of methioninase-induced S/G2-phase-trapping for subsequent effective chemotherapy (2013)
  • Author(s): Shuya Yano, Yasunori Tome, Michelle Digman, Masashi Momiyama, Atsushi Suetsugu, Enrico Gratton, Robert M. Hoffman.
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: Washington DC, （アメリカ）
  • Year and Date: 20130406-20130410
• [Presentation] Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts (2013)
  • Author(s): Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Yukihiko Hiroshima, Itaru Endo, Robert M. Hoffman.
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: Washington DC, （アメリカ）
  • Year and Date: 20130406-20130410
• [Presentation] Imaging exosome transfer from colon cancer cells to stroma at liver metastatic sites in nude mouse (2013)
  • Author(s): Atsushi Suetsugu, Kimi Homma, Shigetoyo Saji, Hisataka Moriwaki, Takahiro Ochiya, Robert M. Hoffman.
  • Organizer: AACR annual meeting 2013
  • Place of Presentation: Washington DC, （アメリカ）
  • Year and Date: 20130406-20130410
• [Presentation] Cell cycle position and chemoresponse depends on location in tumor
  • Author(s): Yasunori Tome, Michelle A. Digman, Masashi Momiyama, Atsushi Suetsugu, Enrico Gratton, Shuya Yano, Robert M. Hoffman
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 東京
• [Presentation] Comparison of Salmonella typhimurium A1-R and chemotherapy of human-patient pancreatic tumorgrafts
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Micheal Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 東京
• [Presentation] 当院におけるC型慢性肝炎に対する3剤併用療法の初期治療効果と副作用の検討
  • Author(s): 末次 淳、宮崎恒起、華井竜徳、今井健二、白木 亮、高井光治、大澤陽介、清水雅仁、内木隆文、森脇久隆
  • Organizer: JDDW2013
  • Place of Presentation: 東京
• [Presentation] HIV感染治療開始後に伴うB型肝炎の免疫再構築症候群の検討
  • Author(s): 末次 淳、宮崎恒起、華井竜徳、今井健二、白木 亮、高井光治、清水雅仁、内木隆文、鶴見寿、森脇久隆
  • Organizer: JDDW2013
  • Place of Presentation: 東京