Generation of cancer stem cell library from iPS cells for development of drug screening system

• Project/Area Number: 24501315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Okayama University
• Principal Investigator: MIZUTANI Akifumi 岡山大学, 自然科学研究科, 助教 (50598331)
• Co-Investigator(Kenkyū-buntansha): SENO Masaharu 岡山大学, 大学院自然科学研究科, 教授 (90243493)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: がん幹細胞 / 薬剤スクリーニング / iPS / ドラッグデリバリー / がん幹細胞ニッチ / エクソソーム / 標的化薬剤 / スクリーニング / アポトーシス / iPS細胞 / 脂肪肉腫 / ニッチ

Outline of Final Research Achievements

In the study of cancer and development of new anticancer drug, cancer stem cells (CSCs) are now considered to be important targets. In this study, we developed a drug screening system using various mouse iPS-derived cancer stem model cells (miPS-CSCs). In addition, we analyzed the gene expression profiles of miPS-CSCs, which focus on cell surface protein to use targeted drug delivery system. Comparison with normal tissue distribution, we nominated several candidate genes for tissue specific targeting.

Research Products

• [Journal Article] Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles (2014)
  • Author(s): Yan T, Mizutani A, Chen L, Takaki M, Hiramoto Y, Matsuda S, Shigehiro T, Kasai T, Kudoh T, Murakami H, Masuda J, Hendrix MJ, Strizzi L, Salomon DS, Fu L, Seno M.
  • Journal Title: Journal of Cancer Volume: 5 Issue: 7 Pages: 572-584
  • DOI: 10.7150/jca.8865
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cancer stem cells maintain a hierarchy of differentiation by creating their niche. (2013)
  • Author(s): Matsuda S, Yan T, Mizutani A, Sota T, Hiramoto Y, Prieto-Vila M, Chen L, Satoh A, Kudoh T, Kasai T, Murakami H, Fu L, Salomon DS, Seno M
  • Journal Title: Int J Cancer Volume: 00 Issue: 1 Pages: 0-0
  • DOI: 10.1002/ijc.28648
  • Peer Reviewed / Open Access
• [Journal Article] A cancer stem cell model: an insight into the conversion of induced pluripotent stem cells to cancer stem-likecells. (2013)
  • Author(s): Mizutani A, Chen L, Kasai T, Kudoh T, Murakami H, Fu L, Seno M
  • Journal Title: Cancer Stem Cells (Ed. Rajasekhar K. Vinagolu), Wiley-Blackwell Volume: 未定
• [Journal Article] Cancer stem cells derived from mouse induced pluripotent stem cells. (2013)
  • Author(s): Murakami H, Mizutani A, Chen L, Kasai T, Kudoh T, Fu L, Seno M.
  • Journal Title: Stem cells and cancer stem cells (Ed. M.A. Hayat), Springer Volume: 未定
  • Peer Reviewed
• [Journal Article] マウスiPS細胞から作るがん幹細胞モデル (2013)
  • Author(s): 笠井智成，陳 凌，工藤孝幸，水谷昭文，妹尾昌治
  • Journal Title: 細胞工学 Volume: 32 Pages: 330-330
• [Journal Article] A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells (2012)
  • Author(s): Ling Chen, Masashi Okada, et al
  • Journal Title: PLoS ONE Volume: 7 Issue: 4 Pages: e33544-e33544
  • DOI: 10.1371/journal.pone.0033544
  • Peer Reviewed
• [Presentation] がん幹細胞ニッチにおけるがん幹細胞の自己複製制御機構の解析 (2014)
  • Author(s): 平本祐樹、渡邉直哉、松田修一、Yan T、Marta P Vila、水谷昭文、村上宏、笠井智成、妹尾昌治
  • Organizer: 第37 回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] Tumor derived exosome/microvesicles convert mouse iPS cells to cancer stem-like cells (2014)
  • Author(s): Yan T, Mizutani A, Chen L, Murakami H, Seno M
  • Organizer: 第73 回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Tumor derived exosomes/microvesicles convert mouse induced pluripotent stem cells to cancer stem cells (2014)
  • Author(s): Yan T, Mizutani A, Chen L, Murakami H, Seno M
  • Organizer: Exosomes & Single cell Analysis Summit
  • Place of Presentation: アメリカ サンディエゴ
  • Year and Date: 2014-09-18 – 2014-09-19
• [Presentation] Cancer stem cells maintain a hierarchy of differentiation by creating their niche (2014)
  • Author(s): Mizutani A, Matsuda S, Yan T, Prieto-Vila M, Chen L, Satoh A, Kasai T, Masuda J, Kudoh T, Murakami H, Fu L, Salomon DS, Seno M
  • Organizer: AACR Annual meeting 2014
  • Place of Presentation: アメリカ サンディエゴ
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived exosomes/microvesicles (2014)
  • Author(s): Yan T, Masuda J, Mizutani A, Chen L, Shigehiro T, Matsuda S, Kasai T, Kudoh T, Murakami H, Hendrix MJ, Strizzi L, Salomon DS, Seno M
  • Organizer: AACR Annual meeting 2014
  • Place of Presentation: アメリカ サンディエゴ
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Cancer stem cells maintain a hierarchy of differentiation by creating their niche (2014)
  • Author(s): Matsuda S, Ting Y, Mizutani A, Murakami H, Seno M
  • Organizer: 第7回高度医療都市を創出する未来科学技術国際シンポジウム
  • Place of Presentation: 岡山
• [Presentation] In vitro niche created by cancer stem-like cells derived from mouse induced pluripotent stem cell (2013)
  • Author(s): Mizutani A, Matsuda S, Ting Y, Sota T, Kasai T, Murakami H, Kudou T, Seno M
  • Organizer: American Association for Cancer Research Anuual Meeting 2013
  • Place of Presentation: アメリカ ワシントンDC
• [Presentation] Characterization of cancer stem-like cell converted from mouse iPS cell by tumor derived exosome/microvesicle (2013)
  • Author(s): Ting Y, Mizutani A, Chen L, Hiramoto Y, Takaki M, Murakami H, Seno M
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Characterization of cancer stem-like cell converted from mouse iPS cell by tumor derived exosome/microvesicle (2013)
  • Author(s): Ting Y, 水谷昭文、村上宏、妹尾昌治
  • Organizer: 第17回生体触媒化学シンポジウム
  • Place of Presentation: 岡山
• [Presentation] An insight into cancer stem cells through a cancer stem cell model developed from mouse iPSCs (2013)
  • Author(s): M. Seno, L. Chen, T. Kudoh, T. Kasai, H. Murakami, A. Mizutani
  • Organizer: 19th Internatinal Charles Heidelberger SYmposiumu on Cancer Research
  • Place of Presentation: 鹿児島
  • Invited
• [Presentation] miPS-CSC maintains self-renewal and differentiation capacity in vitro by creating a niche (2013)
  • Author(s): T. Yan, S. Matsuda, A. Mizutani, H. Murakami, M. Seno
  • Organizer: The 6th International symposium for future technology creating better human health and society
  • Place of Presentation: 岡山
• [Presentation] マウス人工多能性幹細胞より誘導したがん幹細胞モデルの生体外解析 (2012)
  • Author(s): 松田修一、水谷昭文、笠井智成、佐藤あやの、工藤孝幸、陳凌、妹尾昌治
  • Organizer: 日本癌学会 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Cancer stem-like cells derived from mouse induced pluripotent stem cell create a niche to promote self-renewal by themselves (2012)
  • Author(s): T.Yan, S.Matsuda, M.Prieto Vila, A.Mizutani, H.Murakami, M.Seno
  • Organizer: 日本分子生物学会 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Patent(Industrial Property Rights)] がん幹細胞及びその用途 (2014)
  • Inventor(s): 妹尾昌治、水谷昭文、笠井智成
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-014778
  • Filing Date: 2014-01-29
• [Patent(Industrial Property Rights)] がん幹細胞を含む細胞集団を得る方法 (2014)
  • Inventor(s): 妹尾昌治、水谷昭文、笠井智成
  • Industrial Property Rights Holder: 岡山大学、LSIPファンド運営合同会社
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-19
  • Overseas
• [Patent(Industrial Property Rights)] 不均一ながん幹細胞及びその用途 (2013)
  • Inventor(s): 妹尾昌治、水谷昭文、笠井智成
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-27
• [Patent(Industrial Property Rights)] CANCER CELLS AND APPLICATION THEREOF (2013)
  • Inventor(s): Masaharu Seno
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-03-19
  • Overseas