Molecular mechanisms of differentiation and metastasis of human gastrointestinal cancer stem cells

• Project/Area Number: 15K08970
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyushu University
• Principal Investigator: Baba Eishi 九州大学, 医学研究院, 教授 (00315475)
• Co-Investigator(Kenkyū-buntansha): 有山 寛 九州大学, 大学病院, 助教 (80713437)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 大腸癌 / 胃癌 / 癌幹細胞 / 組織幹細胞 / オルガノイド / 上皮間葉転換 / 印環細胞癌 / 消化器癌 / スフェア

Outline of Final Research Achievements

Freshly isolated human gastrointestinal cancer stem cells (CSCs) and normal tissue stem cells, which form organoid in our culture system, were examined by comprehensive gene expression analysis. Differentiated colorectal non-CSCs in the culture were demonstrated to retrieve the stem cell features in association with activation of TWIST1, a key molecule of epithelial-mesenchymal transition process. Normal gastric tissue stem cells-derived organoid exhibited signet-ring cell carcinoma-like morphology by inhibition of E-cadherin expression. These molecules regulating the behavior of CSCs and tissue stem cells could possibly become therapeutic targets for cancer chemotherapy.

Research Products

• [Journal Article] Colorectal cancer stem cell population consist of heterogeneous cells based on E-cadherin expression with different tumorigenic potential in vivo (2018)
  • Author(s): Tamura S, Isobe T, Ariyama H, Nakano M, Kikushige Y, Takaishi S, Kusaba H, Takenaka K, Ueki T, Nakamura M, Akashi K, Baba E
  • Journal Title: Oncol Rep Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Weight loss during initial chemotherapy predicts survival in patients with advanced gastric cancer (2017)
  • Author(s): Takayoshi K, Uchino K, Nakano M, Ikejiri K, Baba E
  • Journal Title: Nutr Cancer Volume: 69 Pages: 408-415
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Efficacy and safety analysis of oxaliplatin-based chemotherapy for advanced gastric cancer with a prior treatment of cisplatin (2017)
  • Author(s): Inadomi K, Kusaba H, Matsushita Y, Tanaka R, Mitsugi K, Arimizu K, Hirano G, Makiyama A, Ohmura H, Uchino K, Hanamura F, Shibata Y, Kuwayama M, Esaki T, Takayoshi K, Arita S, Ariyama H, Akashi K, Baba E
  • Journal Title: Anticancer Res Volume: 7 Pages: 2663-2671
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer (2017)
  • Author(s): Makiyama A, Arimizu K, Hirano G, Makiyama C, Matsushita Y, Shirakawa T, Ohmura H, Komoda M, Uchino K, Inadomi K, Arita S, Ariyama H, Kusaba H, Shinohara Y, Kuwayama M, Kajitani T, Oda H, Esaki T, Akashi K, Baba E
  • Journal Title: Gastric Cancer Volume: - Issue: 3 Pages: 464-472
  • DOI: 10.1007/s10120-017-0759-9
  • NAID: 40021539459
  • Peer Reviewed / Int'l Joint Research
• [Presentation] マウス胃組織幹細胞の同定および印環細胞癌発癌マウスモデルの構築 (2017)
  • Author(s): 有山寛、早河翼、馬場英司、赤司浩一、Timothy C. Wang
  • Organizer: 第89回日本胃癌学会総会
• [Presentation] 胃組織幹細胞と印環細胞癌発癌モデルマウス (2017)
  • Author(s): 有山寛、早河翼、馬場英司、赤司浩一、Timothy C. Wang
  • Organizer: 第27回日本サイトメトリー学会学術集会
• [Presentation] 胃印環細胞癌における癌幹細胞とニッチ (2017)
  • Author(s): 有山寛、早河翼、馬場英司、赤司浩一、Timothy C. Wang
  • Organizer: 胃印環細胞癌における癌幹細胞とニッチ
• [Presentation] Tumor infiltrating lymphocytes in malignant ascites predict prognosis of gastrointestinal cancer (2017)
  • Author(s): 第76回日本癌学会学術集会
  • Organizer: 中野倫孝、伊東守、田中吏佐、稲富享子、三ツ木健二、土橋賢司、有山寛、草場仁志、赤司浩一、馬場英司
• [Presentation] 癌性腹水中TILは疲弊マーカーを高頻度で発現する (2017)
  • Author(s): 中野倫孝、伊東守、田中吏佐、稲富享子、三ツ木健二、土橋賢司、有山寛、草場仁志、赤司浩一、馬場英司
  • Organizer: 第15回日本臨床腫瘍学会学術集会
• [Presentation] The risk factors for oxaliplatin-induced thrombocytopenia and neuropathy in advanced gastric cancer (2017)
  • Author(s): Kyoko Inadomi, Hitoshi Kusaba, Akitaka Makiyama, Kenji Mitsugi, Keita Uchino, Shingo Tamura, Yoshihiro Shibata, Taito Esaki, Kenji Tsuchihashi, Shuji Arita, Hiroshi Ariyama, Eishi Baba
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] TGF-beta regulates CD44 expression of cancer cells through epithelial-to-mesenchymal transition in malignant ascites (2016)
  • Author(s): Michitaka Nakano, Hiroshi Ariyama, Eishi Baba, et al.
  • Organizer: 第14回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-07-28
• [Presentation] Transition of macrophage to fibroblast promote cancer progression in malignant ascites environment within gastrointestinal peritoneal carcinomatosis patients. (2016)
  • Author(s): Mamoru Ito, Hiroshi Ariyama, Eishi Baba, et al.
  • Organizer: AACR2016
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] 悪性腹水中がん細胞のCD44の発現は可塑性をもち、TGF-betaシグナルが関与している (2015)
  • Author(s): 中野倫孝、田中守、田中吏佐、高吉琴絵、熊谷穂積、稲富享子、在田修二、牧山明資、江崎泰斗、三ツ木健二、草場仁志、馬場英司
  • Organizer: 第74回日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-09
• [Presentation] EMT induces sphere forming ability in primary colorectal cancer (2015)
  • Author(s): Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Takashi Ueki, Eishi Baba, Koichi Akashi
  • Organizer: 第13回幹細胞シンポジウム
  • Place of Presentation: 東京大学
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] Plasticity of CD44+ colorectal cancer cell depends on TGF-beta induced EMT (2015)
  • Author(s): Michitaka Nakano, Hiroshi Ariyama, Shingo Tamura, Taichi Isobe, Kohta Miyawaki, Yuta Okumura, Hitoshi Kusaba, Takashi Ueki, Eishi Baba, Koichi Akashi
  • Organizer: AACR annual meeting 2015
  • Place of Presentation: Pennsylvania
  • Year and Date: 2015-04-20
  • Int'l Joint Research