Identification of pancreatic cancer stem cell lineage during pancreatic tumorigenesis

• Project/Area Number: 24390305
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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): TANIGUCHI Hideki 横浜市立大学, 医学研究科, 教授 (70292555) ; TAKEBE Takanori 横浜市立大学, 医学部, 准教授 (20612625)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 癌 / 細胞・組織 / 膵癌幹細胞 / 膵癌 / 癌幹細胞 / 転移 / がん幹細胞 / 膵臓

Outline of Final Research Achievements

Pancreatic cancer tissues were harvested from different carcinogenesis stages of pancreatic model mice. The cells were separated by cell sorter using a specific antibody that recognizes a number of surface antigens known as a cancer stem cell marker. The separated cells were examined either have a capability as cancer stem cells. Cancer stem cells collected from mice with progressed cancer were found to have metastatic potential in addition to the tumor forming potency. Furthermore, pancreatic cancer stem cells with tumor -forming ability that was separated from the carcinogenic early pancreatic cancer tumor tissue does not have a metastatic potential, but the metastatic potential succeed planting cells of pancreatic cancer xenografts, which is formed from this carcinogenesis early cancer stem cells in a xenograft It revealed to exacerbate into cells having .

Research Products

• [Journal Article] Tropism of cancer stem cells to a specific distant organ. (2014)
  • Author(s): Okuda R, Sekine K, Hisamatsu D, Ueno Y, Takebe T, Zheng YW, Taniguchi H.
  • Journal Title: In vivo. Volume: 28 Pages: 361-365
  • Peer Reviewed
• [Journal Article] Polycomb group protein Ezh2 regulates hepatic progenitor cell proliferation and differentiation in murine embryonic liver. (2014)
  • Author(s): Koike H, Ouchi R, Ueno Y, Nakata S, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H.
  • Journal Title: PLoS One. Volume: 9 Issue: 8 Pages: 0-2
  • DOI: 10.1371/journal.pone.0104776
  • Peer Reviewed / Open Access
• [Journal Article] Efficient hepatic differentiation of human induced pluripotent stem cells in a three-dimensional microscale culture. (2014)
  • Author(s): Zhang RR, Takebe T, Miyazaki L, Takayama M, Koike H, Kimura M, Enomura M, Zheng YW, Sekine K, Taniguchi H.
  • Journal Title: Methods Mol Biol. Volume: 1210 Pages: 131-141
  • DOI: 10.1007/978-1-4939-1435-7_10
  • ISBN: 9781493914340, 9781493914357
  • Peer Reviewed
• [Journal Article] Fluorescent labeling and visualization of human induced pluripotent stem cells with the use of transcription activator-like effector nucleases. (2014)
  • Author(s): Sekine K, Takebe T, Taniguchi H.
  • Journal Title: Transplant Proc. Volume: 46 Issue: 4 Pages: 1205-1207
  • DOI: 10.1016/j.transproceed.2014.02.003
  • Peer Reviewed
• [Journal Article] The evidence of sophisticatedly heterogeneous population of human umbilical vein endothelial cells (2014)
  • Author(s): Zheng YW, Nie YZ, Tsuchida T, Zhang RR, Aoki K, Sekine K, Ogawa M, Takebe T, Ueno Y, Sakakibara H, Hirahara F, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46 Issue: 4 Pages: 1251-3
  • DOI: 10.1016/j.transproceed.2013.11.077
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Proliferating Human Hepatic Cells from Human Induced Pluripotent Stem Cells (2014)
  • Author(s): Zhang RR, Takebe T, Sekine K, Koike H, Zheng YW, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46(4) Issue: 4 Pages: 1201-4
  • DOI: 10.1016/j.transproceed.2013.12.021
  • Peer Reviewed
• [Journal Article] The development of humanized liver with Rag1 knockout rats. (2014)
  • Author(s): Tsuchida T, Zheng YW, Zhang RR, Takebe T, Ueno Y, Sekine K, Taniguchi H
  • Journal Title: Transplant Proc Volume: 46 Issue: 4 Pages: 1191-3
  • DOI: 10.1016/j.transproceed.2013.12.026
  • Peer Reviewed / Open Access
• [Journal Article] High-resolution intravital imaging for monitoring the transplanted islets in mice. (2014)
  • Author(s): Takahashi Y, Takebe T, Enomura M, Koike N, Lee S, Nemeno JG, Sekine K, Lee JI, Taniguchi H.
  • Journal Title: Transplant Proc. Volume: 46 Issue: 4 Pages: 1166-1168
  • DOI: 10.1016/j.transproceed.2013.11.089
  • Peer Reviewed
• [Journal Article] The CD133+CD44+ Precancerous Subpopulation of Oval Cells is a Therapeutic Target for Hepatocellular Carcinoma (2014)
  • Author(s): Zheng YW, Tsuchida T, Shimao T, Li B, Takebe T, Zhang RR, Sakurai Y, Ueno Y, Sekine K, Ishibashi N, Imajima M, Tanaka T, and Taniguchi H
  • Journal Title: Stem Cells Dev Volume: (In press) Issue: 18 Pages: 2237-2249
  • DOI: 10.1089/scd.2013.0577
  • Peer Reviewed / Open Access
• [Journal Article] Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion via Simultaneous Suppression of Cdkn1a and Cdkn2a. (2014)
  • Author(s): Koike H, Ueno Y, Naito T, Shiina T, Nakata S, Ouchi R, Obana Y, Sekine K, Zheng YW, Takebe T, Isono K, Koseki H, Taniguchi H
  • Journal Title: Hepatology Volume: 印刷中 Issue: 1 Pages: 323-333
  • DOI: 10.1002/hep.27046
  • Peer Reviewed / Open Access
• [Journal Article] Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant. (2014)
  • Author(s): Takanori Takebe*, Ran-Ran Zhang, Hiroyuki Koike, Masaki Kimura, Emi Yoshizawa, Masahiro Enomura, Keisuke Sekine, Hideki Taniguchi*(*: Correspondence)
  • Journal Title: Nature Protocols Volume: 9(2) Issue: 2 Pages: 396-409
  • DOI: 10.1038/nprot.2014.020
  • Peer Reviewed
• [Journal Article] Engineering of human hepatic tissue with functional vascular networks (2014)
  • Author(s): Takebe T, Koike N, Sekine K, Fujiwara R, Amiya T, Zheng YW and Taniguchi H
  • Journal Title: Organogenesis Volume: 10(2)(Epub ahead of print) Issue: 2 Pages: 260-267
  • DOI: 10.4161/org.27590
  • Peer Reviewed
• [Journal Article] Tropism of cancer stem cells to a specific distant organ (2014)
  • Author(s): Okuda R, Sekine K, Hisamatsu D, Ueno Y, Takebe T, Zheng YW, Taniguchi H.
  • Journal Title: In Vivo Volume: in press
  • Peer Reviewed
• [Journal Article] The CD133+CD44+ Precancerous Subpopulation of Oval Cells is a Therapeutic Target for Hepatocellular Carcinoma (2014)
  • Author(s): Zheng YW, Tsuchida T, Shimao T, Li B, Takebe T, Zhang RR, Sakurai Y, Ueno Y, Sekine K, Ishibashi N, Imajima M, Tanaka T, Taniguchi H.
  • Journal Title: Stem Cells Dev. Volume: in press
  • Peer Reviewed
• [Journal Article] Fluorescent labeling and visualization of human induced pluripotent stem cells with the use of transcription activatore like effector nucleases (2014)
  • Author(s): Sekine K, Takebe T, Taniguchi H.
  • Journal Title: Transplant Proc. Volume: in press
  • Peer Reviewed
• [Journal Article] Vascularized and functional human liver from an iPSC-derived organ bud transplant. (2013)
  • Author(s): Takanori Takebe*, Keisuke Sekine, Masahiro Enomura, Hiroyuki Koike, Ran-Ran Zhang, Yasuharu Ueno, Yun-Wen Zheng, Naoto Koike, Shinsuke Aoyama, Yasuhisa Adachi, Hideki Taniguch*(*: Correspondence)
  • Journal Title: Nature Volume: 499 Issue: 7459 Pages: 481-484
  • DOI: 10.1038/nature12271
  • NAID: 40020351046
  • Peer Reviewed
• [Journal Article] The generation of pancreatic β-cell spheroids in a simulated microgravity culture system. (2013)
  • Author(s): Tanaka H
  • Journal Title: Biomaterials Volume: 34 Issue: 23 Pages: 5785-5791
  • DOI: 10.1016/j.biomaterials.2013.04.003
  • Peer Reviewed
• [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Naka michi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
  • Journal Title: Endocrinology. Volume: 154 Issue: 3 Pages: 1008-20
  • DOI: 10.1210/en.2012-1542
  • Peer Reviewed
• [Journal Article] Establishment of Automated Culture System for Murine Induced Pluripotent Stem Cells (2012)
  • Author(s): Koike H
  • Journal Title: BMC Biotechnology Volume: 12 Issue: 1 Pages: 81-81
  • DOI: 10.1186/1472-6750-12-81
  • Peer Reviewed
• [Journal Article] Highly efficient generation of definitive endoderm lineage from human induced pluripotent stem cells (2012)
  • Author(s): Sekine K
  • Journal Title: Transplant Proc Volume: 44(4) Issue: 4 Pages: 1127-1129
  • DOI: 10.1016/j.transproceed.2012.03.001
  • Peer Reviewed
• [Journal Article] Regenerative medicine approach as an alternative treatment to islet transplantation. (2012)
  • Author(s): Sekine K
  • Journal Title: Transplant Proc Volume: 44(4) Issue: 4 Pages: 1104-1106
  • DOI: 10.1016/j.transproceed.2012.03.020
  • Peer Reviewed
• [Journal Article] Self-organization of human hepatic organoid by recapitulating organogenesis in vitro (2012)
  • Author(s): Takebe T
  • Journal Title: Transplant Pro Volume: 44(4) Issue: 4 Pages: 1018-1020
  • DOI: 10.1016/j.transproceed.2012.02.007
  • Peer Reviewed
• [Journal Article] Generation of functional human vascular network in vitro (2012)
  • Author(s): Takebe T
  • Journal Title: Transplant Proc Volume: 44(4) Issue: 4 Pages: 1130-1133
  • DOI: 10.1016/j.transproceed.2012.03.039
  • Peer Reviewed
• [Journal Article] Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis (2012)
  • Author(s): Hirose, Y., Saijou, E., Sugan,o Y., Takeshita, F., Nishimura, S., Nonaka, H., Chen, Y.R., Sekine, K., Kido, T., Nakamura, T., Kato, S., Kanke, T., Nakamura, K., Nagai, R., Ochiya, T., Miyajima, A.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 109 Issue: 11 Pages: 4263-4268
  • DOI: 10.1073/pnas.1117560109
  • Peer Reviewed
• [Journal Article] Basics and applications of stem cells in the pancreas (2012)
  • Author(s): Sekine K, Taniguchi H
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 19 Issue: 6 Pages: 594-599
  • DOI: 10.1007/s00534-012-0545-3
  • NAID: 10031126973
• [Presentation] 膵癌転移における微小環境と癌幹細胞の相互作用の解析 (2015)
  • Author(s): 濱中香織、奥田諒、関根圭輔、谷口英樹
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2015-03-21
• [Presentation] 膵癌幹細胞の転移における特定臓器への指向性 (2015)
  • Author(s): 泉陽彦、竹歳卓人、関根圭輔、奥田諒、濱中香織、谷口英樹
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2015-03-21
• [Presentation] A novel system with human liver features for screening anti-hepatitis B virus therapeutics (2015)
  • Author(s): Nie YZ,Zheng YW,kZhang RR,Tsuchida T,Ueno Y、Sekine K,Takebe T,Taniguchi H
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2015-03-20
• [Presentation] iPS細胞を用いた代謝性臓器の再生医療 (2015)
  • Author(s): 武部貴則、関根圭輔、谷口英樹
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2015-03-19
  • Invited
• [Presentation] 遺伝子改変モデル動物を用いた膵癌幹細胞の機能解析 (2014)
  • Author(s): 関根圭輔、奥田諒、久松大介、濱中香織、谷口英樹
  • Organizer: 第41回日本臓器保存生物医学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪府)
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] Identification and characterization of Pdx1+ pancreatic cancer stem cell during pancreatic tumorigenesis (2014)
  • Author(s): 関根圭輔、奥田諒、久松大介、谷口英樹
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2014-09-25
• [Presentation] Identification of pancreatic cancer stem cell lineage during pancreatic tumorigenesis (2014)
  • Author(s): 奥田諒、関根圭輔、久松大介、孫略、濵中香織、谷口英樹
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2014-09-25
• [Presentation] スフィア形成能を有する膵癌幹細胞の解析 (2014)
  • Author(s): 久松大介、奥田諒、関根圭輔、濵中香織、上野康晴、谷口英樹
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2014-09-25
• [Presentation] 膵癌幹細胞の系譜解析に向けたin vitroアッセイ系の構築 (2014)
  • Author(s): 久松大介、奥田 諒、関根圭輔、上野康晴、谷口英樹
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Pdx1陽性細胞は高い腫瘍形成能とスフィア形成能を有する癌幹細胞である (2013)
  • Author(s): 奥田諒、関根圭輔、孫略、坪井康次、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
• [Presentation] 膵幹/前駆細胞の膵癌幹細胞への形質転換プロセスの解析 (2013)
  • Author(s): 関根圭輔、孫略、奥田諒、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
• [Presentation] ヒト膵癌幹細胞における治療抵抗性機構の解析 (2013)
  • Author(s): 12. 星野小百合、関根圭輔、孫略、中田晋、寺崎哲也、森永総一郎、宮城洋平、遠藤格、横瀬智之、倉田昌直、上野康晴、谷口英樹
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
• [Presentation] Targeted proteomic absolute quantification on transporters of human pancreatic cancer cells with gemcitabine-resistance. (2013)
  • Author(s): Ueno Y, Hoshino S, Tsuchida N, Nakata S, Uchida Y, Sekine K, Zheng YW, Kurata M, Morinaga S, Miyagi Y, Yokose T, Endo I, Terasaki T, Hirano H, Taniguchi H
  • Organizer: HUPO 12th annual world congress.
  • Place of Presentation: パシフィコ横浜(神奈川)
• [Presentation] ヒトiPSを用いたファーマコセロミクス基盤技術の開発 (2012)
  • Author(s): 谷口英樹, 武部貴則, 関根圭輔, 青山晋輔, 安達弥永
  • Organizer: 第127回日本薬理学会関東部会シンポジウム
  • Place of Presentation: 東京国際フォーラム(東京)(招待講演)
  • Year and Date: 2012-10-20
• [Presentation] 膵幹細胞を起点とした膵発癌プロセスにおける膵癌幹細胞の細胞系譜的解析 (2012)
  • Author(s): 関根圭藍, 孫略, 上野康晴, 谷口英樹
  • Organizer: 第22回日本サイトメトリー学会
  • Place of Presentation: 千里ライフサイエンスセンター(大阪府)
  • Year and Date: 2012-06-30
• [Presentation] 膵癌モデルマウスを用いた膵癌幹細胞の細胞系譜解析 (2012)
  • Author(s): 関根圭輔, 孫略, 奥田諒, 谷口英樹
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(札幌)
• [Presentation] 膵肝/前駆細胞の膵癌幹細胞への形質転換プロセスの解析 (2012)
  • Author(s): 孫略, 奥田諒, 関根圭輔, 盛武敬, 坪井康次, 谷口英樹
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
• [Presentation] 膵癌幹細胞のin vitroアッセイ系の解析 (2012)
  • Author(s): 奥田諒, 孫略, 関根圭輔, 松井智栄美, 坪井康次, 谷口英樹
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場(福岡県)
• [Presentation] Identification of pancreatic stem/progenitor cells expres sing PDX1 reside in the CD133 positive pancreatic duet. (2012)
  • Author(s): Sekine K, Ishikawa M, Takebe T, Suzaki A, Kawashimo K, Matsui C, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting.
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Creation of vascularized human organ from induced piuripotent stem cells. (2012)
  • Author(s): Takebe T, Sekine K, Enomura M, Suzuki Y, Koike H, Zhang R, Koike N, Ueno Y, Zheng Y, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Generation of islet like structures with human functional vascular networks. (2012)
  • Author(s): Enomura M, Takebe T, Sekine K, Koike N, Taniguchi H, Tanaka H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Self-renewal versus differentiation as well as the liver repopulation capability of human hepatic stem cells. (2012)
  • Author(s): Zheng Y, Li B, Zhang R, Kimura M, Tsuchida T, Takebe T, Ueno Y, Sekine K, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Identification of pancreatic stem/progenitor cells expres sing PDX1 reside in the CD133 positive pancreatic due (2012)
  • Author(s): Sekine K, Ishikawa M, Takebe T, Suzaki A, Kawashimo K, Matsui C, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting.
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] 膵幹細胞を起点とした膵発癌プロセスの細胞系譜的解析 (2012)
  • Author(s): 関根圭輔, 松井智栄美, 孫略, 長久紗耶佳, 田中慎, 武部貴則, 谷口英樹
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] 多能性幹細胞を用いた機能的なヒト臓器の創出 (2012)
  • Author(s): 武部貴則, 関根圭輔, 江野村允宏, 小池博之, 張冉冉, 三橋優澄, 上野康晴, 鄭允文, 谷口英樹
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] 多能性幹細胞を用いた機能的なヒト臓器の創出 (2012)
  • Author(s): 武部貴則, 関根圭輔, 江野村允宏, 小池博之, 張冉冉, 木村昌樹, 魚返拓則, 吉澤絵美, 川又史佳, 上野康晴, 鄭允文, 小池直人, 谷旦英樹
  • Organizer: 第39回日本臓器保存生物医学会学術集会
  • Place of Presentation: コラッセふくしま(福島県)
• [Presentation] ヒト微小血管網を有する膵島様組織の創出 (2012)
  • Author(s): 高橋禎暢, 江野村允宏, 武部貴則, 関根圭輔, 小池直人, 田中寛康, 谷口英樹
  • Organizer: 第39回日本臓器保存生物医学会学術集会
  • Place of Presentation: コラッセふくしま(福島県)