Identification of epigenetic characteristics of Cancer-associated fibroblasts

• Project/Area Number: 16K19959
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: Maeda Masahiro 国立研究開発法人国立がん研究センター, 研究所, 研究員 (30738703)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: がん関連線維芽細胞 / H3K27me3 / WNT5A / エピジェネティクス / ヒストン修飾

Outline of Final Research Achievements

Cancer-associated fibroblasts (CAFs), a major cellular component of cancer stroma, play a crucial role in cancer progression. In this study, we aimed to identify epigenetic characteristics of CAFs, which may underlie stable tumor-promoting capacities of CAFs. Primary culture of CAFs and non-CAFs was established from gastric surgical specimens. Focusing on H3K27me3, a repressive histone mark that is stable and essential for cell-specific differentiation, we revealed that CAFs had genome-wide alterations of H3K27me3, leading to aberrant production of various tumor promoting factors due to decreased H3K27me3. Among them, we identified WNT5A as a therapeutic target derived from CAFs. This study suggested that epigenetic alterations may determine CAF's biological behaviors.

Research Products

• [Journal Article] Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3 (2020)
  • Author(s): Maeda M, Takeshima H, Iida N, Hattori N, Yamashita S, Moro H, Yasukawa Y, Nishiyama K, Hashimoto T, Sekine S, Ishii G, Ochiai A, Fukagawa T, Katai H, Sakai Y, Ushijima T
  • Journal Title: Gut Volume: 69 Pages: 243-251
  • DOI: 10.1136/gutjnl-2018-317645
  • Peer Reviewed / Open Access
• [Presentation] Epigenetic Approaches Provide A Novel Risk Diagnosis and A Therapeutic Strategy for Gastric Cancer (2018)
  • Author(s): 前田将宏, 牛島俊和
  • Organizer: 第90回日本胃癌学会総会
• [Presentation] Therapeutic targets from cancer-associated fibroblasts identified by epigenetic approach (2017)
  • Author(s): Masahiro Maeda, Hideyuki Takeshima, Naoko Iida, Hiroshi Moro, Naoko Hattori, Genichiro Ishi, Atsushi Ochiai, Hitoshi Katai, Yoshiharu Sakai and Toshikazu Ushijima.
  • Organizer: 第89回日本胃癌学会総会
  • Place of Presentation: 広島国際会議場（広島市、広島）
  • Year and Date: 2017-03-08
• [Presentation] Identification of therapeutic targets from cancer-associated fibroblasts by using an epigenetic approach (2017)
  • Author(s): Masahiro Maeda, Hideyuki Takeshima, Naoko Iida, Naoko Hattori, Satoshi Yamashita, Akiko Mori, Hiroshi Moro, Genichiro Ishii, Atsushi Ochiai, Hitoshi Katai, Yoshiharu Sakai, and Toshikazu Ushijima
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Epigenetic alterations are frequent in cancer-associated fibroblasts (2017)
  • Author(s): Hiroshi Moro, Masahiro Maeda, Hideyuki Takeshima, Naoko Iida, Naoko Hattori, Genichiro Ishi, Atsushi Ochiai, Toshikazu Ushijima
  • Organizer: 12th International Gastric Cancer Congress
  • Int'l Joint Research
• [Presentation] Identifying The Therapeutic Targets of Gastric Cancer Using Epigenetic Alternation of Cancer Associated Fibroblasts (2017)
  • Author(s): Hiroshi Moro, Masahiro Maeda, Hideyuki Takeshima, Naoko Iida, Naoko Hattori, Satoshi Yamashita, Toshikazu Ushijima
  • Organizer: 第11回エピジェネティック研究会年会
• [Presentation] エピゲノム変化探索によるがん関連線維芽細胞（CAF）由来の新規治療標的の同定 (2016)
  • Author(s): 前田将宏, 竹島秀幸, 飯田直子, 服部奈緒子, 石井源一郎, 茂呂浩史, 落合淳志, 岡部寛, 坂井義治, 牛島俊和
  • Organizer: 第27回日本消化器癌発生学会総会
  • Place of Presentation: 城山観光ホテル（鹿児島市、鹿児島）
  • Year and Date: 2016-09-15
• [Presentation] Epigenetic alterations are frequent in cancer-associated fibroblasts. (2016)
  • Author(s): Maeda M, Takeshima H, Ishi G, Ochiai A, Hattori N and Ushijima T.
  • Organizer: The 41st Naito Conference
  • Place of Presentation: CHATERAISE Gateaux Kingdom SAPPORO（北海道、札幌）
  • Year and Date: 2016-07-05
• [Presentation] がん関連線維芽細胞には多くのエピジェネティック異常が存在する (2016)
  • Author(s): 前田将宏, 竹島秀幸, 飯田直子, 石井源一郎, 服部奈緒子, 落合淳志, 牛島俊和
  • Organizer: 第10回日本エピジェネティクス研究会年会
  • Place of Presentation: 千里ライフサイエンスセンター（豊中市、大阪）
  • Year and Date: 2016-05-19