Establishment of primary culture of gastrointestinal tumor for clinical application

• Project/Area Number: 17K16542
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Fujino Shiki 大阪大学, 医学系研究科, 特任助教(常勤) (10768956)
• Research Collaborator: Miyoshi Norikatsu ; Ito Aya ; Saso Kazuhiro ; Sasaki Masaru ; Matsuura Nariaki ; Ohue Masayuki ; Yasui Masayoshi ; Mori Masaki ; Doki Yuichiro
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 初代培養 / 癌 / 大腸癌 / 個別化医療 / 薬剤感受性 / 幹細胞 / 癌幹細胞 / 癌関連維芽細胞 / ミニチュアモデル

Outline of Final Research Achievements

Tumors and primary cultured cells show phenotypic heterogeneity, and two-dimensional (2D) cultured cells are useful for various assays used to study these cells. In this study, we developed a primary cultured organoid in 2D culture (2D organoid; 2DO) that maintained the clinical phenotypic heterogeneity of tumor samples. The parental tumor differentiation was preserved in our system, with gene expression similar to that in the parental tumor. In vitro drug sensitivity analysis can be conducted using the 2DO to reflect individual clinical courses. The 2DO developed in this study is an in vitro personal cancer model. This approach may be useful for producing clinical chemotherapy agents as personalized medicines.

Academic Significance and Societal Importance of the Research Achievements

我々の樹立した初代培養細胞は基本的な培養方法を２次元培養としており（two-dimensional (2D) cultured organoid, 2DO）、非常に汎用性がある手法で、薬剤感受性試験を含む様々な研究手法において簡便に用いることができるマテリアルである。２DOを用いることで、より臨床の腫瘍に近い細胞挙動の解析が行え、多くのがん研究や個別化医療における有用なソースとなり得る。

Research Products

• [Journal Article] Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics (2019)
  • Author(s): Fujino, S., Ito, A., Ohue, M., Yasui, M., Mizushima, T., Doki, Y., Mori, M., Miyoshi, N
  • Journal Title: Biochemical and Biophysical Research Communications Volume: in press Issue: 2 Pages: 332-339
  • DOI: 10.1016/j.bbrc.2019.03.173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oct4 gene expression in primary colorectal cancer promotes liver metastasis. (2019)
  • Author(s): Fujino, S., Miyoshi, N.
  • Journal Title: Stem Cells International Volume: in press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The POU5F1 gene expression in colorectal cancer: a novel prognostic marker. (2018)
  • Author(s): Miyoshi N, Fujino S, Ohue M, Yasui M, Takahashi Y, Sugimura K, Tomokuni A, Akita H, Kobayashi S, Takahashi H, Omori T, Miyata H, Yano M
  • Journal Title: Surg Today Volume: in press Issue: 7 Pages: 709-715
  • DOI: 10.1007/s00595-018-1644-9
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 2D organoid (2DO) as human tumor model for predicting therapeutic effect of anti-cancer drugs (2019)
  • Author(s): Fujino, S., Miyoshi, N., Saso, K., Sasaki, M., Yasui, M., Ohue, M., Takahashi, H., Haraguchi, N., Hata, T., Mastuda, C., Mizushima, T., Mori, M., Doki, Y.
  • Organizer: AACR Annual meeting 2019
  • Int'l Joint Research
• [Presentation] Anti-cancer drug sensitivity assay using in vitro primary cultured cells (2018)
  • Author(s): Fujino, S., Miyoshi, N., Ohue, M., Takahashi, Y., Yasui, M., Mishimura, J., Saso, K., Takahashi, H., Haraguchi, N., Hata, T., Mastuda, C., Mizushima, T., Doki, Y., Mori, M.
  • Organizer: AACR Annual meeting 2018
  • Int'l Joint Research
• [Presentation] Anti-cancer drug sensitivity assay using in vitro primary culture cells (2018)
  • Author(s): Shiki Fujino
  • Organizer: AACR Annual meeting 2018
  • Int'l Joint Research