A novel treatment targeting cancer stem-like cells in esophageal squamous cell carcinoma

• Project/Area Number: 18K07959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hokkaido University
• Principal Investigator: Natsuizaka Mitsuteru 北海道大学, 医学研究院, 客員研究員 (80642446)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 癌幹細胞 / 食道扁平上皮癌 / EGFR阻害剤 / MEK阻害剤 / 治療抵抗性 / FGF / CD44 / オーガノイド

Outline of Final Research Achievements

The authors have identified CD24Low/CD44High cells as cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). Furthermore, the authors have reported that FGF-2/FGFR/Erk pathway has critical roles in regulating CSCs in ESCC. In the present study, they have shown that FGFR/Erk inhibitors decrease CSCs in ESCC and restore sensitivity to anticancer drugs and radiation in experiments using organoid culture system, organotypic 3D culture system and xenograft experiments. FGFR/Erk inhibitors could be used as a novel therapy targeting CSCs in ESCC.

Academic Significance and Societal Importance of the Research Achievements

多くの癌において分子標的薬が実用化されている中、進行食道扁平上皮癌（ESCC）においては有効な分子標的薬が未だ無いのが現状である。本研究は進行ESCC症例に対する集学的な新規治療法開発の萌芽となる可能性がある。また、本研究で用いた食道扁平上皮癌３次元培養、オーガノイド、動物モデルは生体内に近い形での癌細胞の培養がin vitroで可能であり、通常培養法では困難な癌研究を飛躍的に向上させてきた。これらの研究手法により今後のESCC研究のさらなる向上が期待される。

Research Products

• [Journal Article] High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C (2020)
  • Author(s): Kawagishi Naoki、Suda Goki、Kimura Megumi、Maehara Osamu、Shimazaki Tomoe、Yamada Ren、Kitagataya Takashi、Shigesawa Taku、Suzuki Kazuharu、Nakamura Akihisa、Ohara Masatsugu、Umemura Machiko、Nakai Masato、Sho Takuya、Natsuizaka Mitsuteru、Morikawa Kenichi、Ogawa Koji、Kudo Yusuke、Nishida Mutsumi、Sakamoto Naoya
  • Journal Title: Hepatology Research Volume: in press Issue: 6 Pages: 671-681
  • DOI: 10.1111/hepr.13490
  • Peer Reviewed
• [Journal Article] Metformin Regulates the Expression of CD133 Through the AMPK-CEBPβ Pathway in Hepatocellular Carcinoma Cell Lines (2019)
  • Author(s): Maehara Osamu、Ohnishi Shunsuke、Asano Ayaka、Suda Goki、Natsuizaka Mitsuteru、Nakagawa Koji、Kobayashi Masanobu、Sakamoto Naoya、Takeda Hiroshi
  • Journal Title: Neoplasia Volume: 21 Issue: 6 Pages: 545-556
  • DOI: 10.1016/j.neo.2019.03.007
  • Peer Reviewed / Open Access
• [Presentation] FGFR阻害剤およびMEK阻害剤は食道扁平上皮癌(ESCC)がん幹細胞を減少させる (2020)
  • Author(s): 前原経、夏井坂光輝、武田宏司
  • Organizer: 第16回日本消化管学会総会学術集会