Analysis of cancer stem cell of esophagogastric junction

• Project/Area Number: 26460934
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Hirata Yoshihiro 東京大学, 医学部附属病院, 助教 (10529192)
• Co-Investigator(Kenkyū-buntansha): 鈴木 伸三 公益財団法人朝日生命成人病研究所, 消化器科, 消化器部長 (30723746) ; 山田 篤生 東京大学, 医学部附属病院, 助教 (80534932)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃食道接合部 / 癌 / 幹細胞 / 分化誘導

Outline of Final Research Achievements

Esophagogastric junction, like cervix of uterus, is composed of squamous and columnar cells, and known to be highly carcinogenic. However, the cause and mechanism of esophogogastric cancer is largely unsolved. In this study, we have examined the origin and mechanism of mouse gastric squamocolumnar junction (SCJ) tumor. KRAS and TGFbR2 mutation in KRT19+ cells led to invasive tumor specifically at gastric SCJ. This tumor showed columnar cell marker KRT7, squamous cell marker KRT14, and several stem cell markers, such as SOX9 and CD44. Organoid culture of SCJ tumor cells revealed these tumors can survive and grow independently of Wnt, EGF, or Noggin stimulation. In normal mouse, KRT19+ cells are observed in the deep lesion of gastric gland especially at SCJ, showing stem cell property in the lineage tracing experiment. In contrast, Lgr5+ cells did not make SCJ tumor upon KRAS and TGFbR2 mutation, suggesting KRT19+, Lgr5- SCJ gland cells can be the origin of SCJ tumor in our model.

Research Products

• [Presentation] Analysis of cancer initiating cell of squamo-columnar junction (2016)
  • Author(s): Hirata Y, Kinoshita H, Suzuki N, Nakagawa H, Ihara S, Hayakawa Y, Koike K
  • Organizer: アジア環太平洋消化器病学会週間
  • Place of Presentation: 神戸
  • Year and Date: 2016-11-04
  • Int'l Joint Research
• [Presentation] Role of CDH1, TGFbR2, and KRAS mutations in the carcinogenesis of stomach (2015)
  • Author(s): Hirata Y
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: ワシントンDC アメリカ
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] 胃食道接合部癌幹細胞の検討 (2014)
  • Author(s): 平田 喜裕、鈴木 伸三、小池 和彦
  • Organizer: 日本消化器関連学会週間
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23
• [Presentation] Analysis of the origin of squamo-columnar junction tumor in a mouse model (2014)
  • Author(s): Hirata Y
  • Organizer: 米国消化器病学会週間
  • Place of Presentation: シカゴ アメリカ
  • Year and Date: 2014-05-04