Analysis of cancer stem cell niche by using esophageal orgnotypic 3D culture system

• Project/Area Number: 26460933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: Yoshito Komatsu 北海道大学, 大学病院, 准教授 (60333598)
• Co-Investigator(Kenkyū-buntansha): 夏井坂 光輝 北海道大学, 医学研究科, 客員研究員 (80642446)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌幹細胞 / 癌幹細胞ニッチ / EGFR阻害剤 / 食道扁平上皮癌 / CD44 / 3次元培養 / ＣＤ４４ / 三次元培養

Outline of Final Research Achievements

We analyzed cacner stem cell niche of esophageal squamous cell carcinoma (ESCC) by using organotypic 3D culture system. Invasive fronts formed cancer stem cell niche in ESCC and epithelial-mesenchymal transition (EMT) had a pivotal role for maintenance of cancer stem cells. EGF released from fibroblasts induced EMT and cancer stem cells were increased in invasive fronts of ESCC. EGFR inhibitors suppressed EMT and formation of cancer stem cell niche and cancer stem cells were decreased in organotypic 3D culture.

Research Products

• [Journal Article] Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer. (2017)
  • Author(s): Kobayashi T, Ishida J, Shimizu Y, Kawakami H, Suda G, Muranaka T, Komatsu Y, Asaka M, Sakamoto N.
  • Journal Title: Tumour Biol Volume: 39 Issue: 3 Pages: 101042831769454-101042831769454
  • DOI: 10.1177/1010428317694547
  • NAID: 120006318739
  • Peer Reviewed
• [Journal Article] Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent: a pilot study. (2016)
  • Author(s): Mizushima T, Ohnishi S, Shimizu Y, Hatanaka Y, Hatanaka KC, Hosono H, Kubota Y, Natsuizaka M, Kamiya M, Ono S, Homma A, Kato M, Sakamoto N, Urano Y
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 411-411
  • DOI: 10.1186/s12885-016-2421-z
  • NAID: 120005773989
  • Peer Reviewed / Open Access
• [Journal Article] S-1 plus leucovorin versus S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer: a randomised, multicentre, open-label, phase 2 trial. (2016)
  • Author(s): Hironaka S, Sugimoto N, Yamaguchi K, Moriwaki T, Komatsu Y, Nishina T, Tsuji A, Nakajima TE, Gotoh M, Machida N, Bando H, Esaki T, Emi Y, Sekikawa T, Matsumoto S, Takeuchi M, Boku N, Baba H, Hyodo I
  • Journal Title: Lancet Oncol Volume: 17 Issue: 1 Pages: 99-108
  • DOI: 10.1016/s1470-2045(15)00410-6
  • Peer Reviewed
• [Journal Article] EGFR inhibitors prevent induction of cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition. (2015)
  • Author(s): Sato F, Kubota Y, Natsuizaka M, Maehara O, Hatanaka Y, Marukawa K, Terashita K, Suda G, Ohnishi S, Shimizu Y, Komatsu Y, Ohashi S, Kagawa S, Kinugasa H, Whelan KA, Nakagawa H, Sakamoto N.
  • Journal Title: Cancer Biol Ther Volume: 16 Issue: 6 Pages: 933940-933940
  • DOI: 10.1080/15384047.2015.1040959
  • Peer Reviewed
• [Journal Article] A pivotal role of Krüppel-like factor 5 in regulation of cancer stem-like cells in hepatocellular carcinoma. (2015)
  • Author(s): Maehara O, Sato F, Natsuizaka M, Asano A, Kubota Y, Itoh J, Tsunematsu S, Terashita K, Tsukuda Y, Nakai M, Sho T, Suda G, Morikawa K, Ogawa K, Chuma M, Nakagawa K, Ohnishi S, Komatsu Y, Whelan KA, Nakagawa H, Takeda H, Sakamoto N.
  • Journal Title: Cancer Biol Ther Volume: 16 Issue: 10 Pages: 14531461-14531461
  • DOI: 10.1080/15384047.2015.1070992
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] EGFR inhibitors suppress epithelial-mesenchymal transition and diminish cancer stem-like cells in esophageal squamous cell carcinoma (2014)
  • Author(s): Fumiyuki Sato, Mitsuteru Natsuizaka, Shinya Ohashi, Shingo Kagawa, Masaki Kuwatai, Hiroshi Kawakami, Shunsuke Ohnishi, Yoshito Komatsu, Mototsugu Kato, Naoya Sakamoto
  • Organizer: 第73回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] EGFR inhibitors eliminate esophageal cancer stem cells by suppressing epithelial-mesenchymal transition. (2014)
  • Author(s): Natsuizaka M, Kaimila B, Kubota Y, Hatanaka Y, Marukawa K, Terashita K, Sato F, Ohnishi S, Suda G, Ohashi S, Kagawa S, Whelan K, Rustgi AK, Nakagawa H, Sakamoto N.
  • Organizer: Digestive Disease Week and the 115th annual meeting of the American Gastroenterological Association.
  • Place of Presentation: McCormick Place (Chicago, USA)
  • Year and Date: 2014-05-03 – 2014-05-06