Dissecting pancreatic cancer cell evolution at single cell level.

• Project/Area Number: 15H04922
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Yokohama City University
• Principal Investigator: SEKINE Keisuke 横浜市立大学, 医学部, 助教 (00323569)
• Co-Investigator(Kenkyū-buntansha): 武部 貴則 横浜市立大学, 先端医科学研究センター, 教授 (20612625) ; 谷口 英樹 横浜市立大学, 医学研究科, 教授 (70292555)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 膵癌 / オルガノイド / 癌 / 細胞・組織 / 癌幹細胞

Outline of Final Research Achievements

Pancreatic cancer is a refractory cancer with extremely poor prognosis because it has poor characteristic clinical symptoms and it is very difficult to detect early. Even when treatment is performed patient with pancreatic cancer exhibit a high recurrence rate and metastasis rate.
In this study, we developed an in vitro culture system capable of reproducing pancreatic cancer microenvironments with the aim of understanding and controlling the process from the development of pancreatic cancer to acquisition of drug resistance ability and acquisition of metastatic potential. We succeeded in extracting multiple candidate molecules possibly involved in the resistance to treatment against anticancer drugs and possibly involved in intercellular interaction between cancer stem cells and microenvironment.

Research Products

• [Int'l Joint Research] University of Alberta(カナダ)
• [Int'l Joint Research] Max Planck Institute(ドイツ)
• [Int'l Joint Research] 台湾大学(台灣)
• [Int'l Joint Research] MaxPlanck Institute(Germany)
• [Journal Article] Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic (2018)
  • Author(s): Yoshinobu Takahashi, Keisuke Sekine, Tatsuya Kin, Takanori Takebe, Hideki Taniguchi
  • Journal Title: Cell Reports Volume: 6 Issue: 6 Pages: 1620-1629
  • DOI: 10.1016/j.celrep.2018.03.123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids. (2018)
  • Author(s): Zhang R-R, Koido M, Tadokoro T, Ouchi R, Matsuno T, Ueno Y, Sekine K, Takebe T*, Taniguch H
  • Journal Title: Stem Cell Reports Volume: 10 Issue: 3 Pages: 780-793
  • DOI: 10.1016/j.stemcr.2018.01.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multilineage communication regulates human liver bud self-organization from pluripotency. (2017)
  • Author(s): Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S, Kageyama J, Damm G, Seehofer D, Belicova L, Bickle M, Barsacchi R, Okuda R, Yoshizawa E, Kimura M, Ayabe H, Taniguchi H, Takebe T*, Treutlein B
  • Journal Title: Nature Volume: 546 Issue: 7659 Pages: 533-534
  • DOI: 10.1038/nature22796
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells. (2017)
  • Author(s): Takebe T*, Sekine K, Kimura M, Yoshizawa E, Funayama S, Nakanishi N, Hisai T, Kobayashi T, Mori A, Ayano S, Ejiri Y, Amimoto N, Yamazaki Y, Ogawa S, Ishikawa M, Kiyota Y, Ueno Y, Taniguchi H
  • Journal Title: Cell Reports Volume: 21 Issue: 10 Pages: 2661-2670
  • DOI: 10.1016/j.celrep.2017.11.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells (2017)
  • Author(s): Chang Po-Hsiang、Sekine Keisuke、Chao Hsiao-Mei、Hsu Shan-hui、Chern Edward
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 45751-45751
  • DOI: 10.1038/srep45751
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Liver Regeneration Using Cultured Liver Bud (2017)
  • Author(s): Sekine K, Takebe T, Taniguchi H.
  • Journal Title: Methods Mol Biol Volume: 1597 Pages: 207-216
  • DOI: 10.1007/978-1-4939-6949-4_15
  • ISBN: 9781493969470, 9781493969494
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism. (2017)
  • Author(s): Koike H, Zhang RR, Ueno Y, Sekine K, Zheng YW, Takebe T, Taniguchi H.
  • Journal Title: Development Volume: 144(6) Pages: 1018-1024
  • DOI: 10.1242/dev.143032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] ヒトiPSC肝芽の臨床応用に向けた安全性評価手法の確立 (2018)
  • Author(s): 濱田 侑希、関根 圭輔、都築 周作、小林 達也、上野 康晴、武部 貴則、谷口 英樹
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] 血管化膵島移植による革新的糖尿病治療法の確立 (2017)
  • Author(s): 高橋禎暢、武部貴則、小池直人、関根圭輔、谷口英樹
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター(宮城)
  • Year and Date: 2017-03-07
• [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドは薬剤耐性を示す (2017)
  • Author(s): 関根 圭輔、奥田 諒、井上 達也、金子 千夏、碓井 彩華、上野 康晴、谷口 英樹
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 癌微小環境を模倣した患者由来ヒト膵がんオルガノイドの創出 (2017)
  • Author(s): 奥田 諒、関根 圭輔、上野康晴 康晴、佐藤 準也、高橋 正希、井上 達也、金子 千夏、碓井 彩華、谷口 英樹 / 横浜市大・医・臓器再生医学
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 腫瘍微小環境を伴う膵癌オルガノイドは薬剤耐性を示す (2017)
  • Author(s): 碓井 彩華、奥田 諒、関根 圭輔、上野 康晴、佐藤 準也、高橋 正希、井上 達也、金子 千夏、谷口 英樹
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 腫瘍微小環境を伴う膵癌オルガノイドはin vitroで治療抵抗性を示す (2017)
  • Author(s): 金子 千夏 、奥田 諒、関根 圭輔、上野 康晴、佐藤 準也、高橋 正希、井上 達也、碓井 彩華、谷口 英樹
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 上野 康晴、奥田 諒、金子 千夏、碓井 彩華、関根 圭輔、谷口 英樹 (2017)
  • Author(s): 微小環境を伴うヒト膵オルガノイドの再構成に基づく新規膵癌薬剤評価系の構築
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] シングルセルレベルでのiPSC肝芽構成細胞のポピュレーションヘテロジェネイティ解析 (2016)
  • Author(s): 関根 圭輔、J. Gray Camp、Barbara Treutlein、武部 貴則、谷口 英樹
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2016-11-30
• [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドの創出 (2016)
  • Author(s): 奥田諒、関根圭輔、上野康晴、佐藤準也、高橋正希、濱中香織、谷口英樹
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2016-11-30
• [Presentation] 臓器形成におけるヘテロジェネイティの理解と制御 (2016)
  • Author(s): 武部 貴則、関根 圭輔、谷口 英樹
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2016-11-30
• [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドの創出 (2016)
  • Author(s): 奥田 諒、高橋 正希、佐藤 準也、関根 圭輔、上野 康晴、谷口 英樹
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、神奈川
  • Year and Date: 2016-10-06
• [Presentation] De novo generation of organ buds from stem cells (2016)
  • Author(s): Keisuke Sekine
  • Organizer: 21st NAT Congress
  • Place of Presentation: Nantes, France
  • Year and Date: 2016-06-09
  • Int'l Joint Research / Invited
• [Presentation] シングルセルRNAシークエンスによるiPS細胞由来肝細胞のポピュレーション解析 (2016)
  • Author(s): 関根圭輔、J. Gray Camp、Barbara Treutlein、武部 貴則、谷口 英樹
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場(大阪府大阪市)
  • Year and Date: 2016-03-17
• [Presentation] Generation of functional human liver from pluripotent stem cell (2016)
  • Author(s): Keisuke Sekine, Takanori Takebe, Hideki Taniguchi
  • Organizer: German Association for the Study of the Liver (GASL) workshop
  • Place of Presentation: Dusseldorf(ドイツ)
  • Year and Date: 2016-01-21
  • Int'l Joint Research / Invited
• [Presentation] iPS細胞を用いた代謝性臓器の再生医療 (2015)
  • Author(s): 関根圭輔
  • Organizer: 第30回日本整形外科学会基礎学術総会
  • Place of Presentation: 富山市民プラザ(富山県富山市)
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] Pdx1+ cells behave as pancreatic cancer stem cells with high tumorigenicity and metastatic potential (2015)
  • Author(s): Ryo Okuda, Keisuke Sekine, Lue Sun , Kaori Hamanaka, Hideki Taniguchi
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-10-08
• [Presentation] Metastatic tropism of pancreatic cancer stem cells to a specific distant organ. (2015)
  • Author(s): Ryo Okuda, Keisuke Sekine, Kaori Hamanaka, Hideki Taniguchi.
  • Organizer: The Biology of Cancer: Microenvironment, Metastasis & Therapeutics
  • Place of Presentation: New York (米国)
  • Year and Date: 2015-05-12
  • Int'l Joint Research
• [Book] Organ Regeneration Based on Developmental Biology (2017)
  • Author(s): Keisuke Sekine, Takanori Takebe, Hideki Taniguchi
  • Total Pages: 257
  • Publisher: Springer book
  • ISBN: 9789811037665
• [Patent(Industrial Property Rights)] 癌微小環境を再現できる癌組織の再構築法 (2016)
  • Inventor(s): 谷口英樹、関根圭輔、上野康晴、奥田諒、武部貴則
  • Industrial Property Rights Holder: 谷口英樹、関根圭輔、上野康晴、奥田諒、武部貴則
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-03-16
• [Patent(Industrial Property Rights)] 血液細胞を用いた組織・臓器の作製方法 (2015)
  • Inventor(s): 谷口英樹、武部貴則、関根圭輔、鄭允文、聶運中
  • Industrial Property Rights Holder: 谷口英樹、武部貴則、関根圭輔、鄭允文、聶運中
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-24