The role of inflammasome and ASC in pancreatic adenocarcinoma progression

• Project/Area Number: 18K15819
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Ehime University
• Principal Investigator: Koizumi Mitsuhito 愛媛大学, 医学部附属病院, 講師(病院教員) (40748307)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵癌 / ASC

Outline of Final Research Achievements

Although molecular targeted therapies for pancreatic ductal adenocarcinoma (PDAC) have been developed, their therapeutic effects are not sufficient and new therapeutic targets are warranted. In this study, we focused on inflammasome, a protein complex that plays a central role in inflammation, and its important constituent protein, apoptosis-associated speck-like protein containing a CARD (ASC). Compared with other inflammasome constituent proteins, ASC was expressed more in PDAC tissues than in the noncancerous pancreatic tissues. ASCs were expressed in multiple PDAC cell lines as compared to pancreatic ductal epithelial cells. Reducing ASCs of PDAC cell lines suppressed cell growth of cancer cells. This study revealed that ASC contributes to the growth of PDAC. Our findings may lead to the establishment of a new therapeutic method targeting ASC in PDAC.

Academic Significance and Societal Importance of the Research Achievements

膵癌に対する分子標的治療が開発されているが、その治療効果は十分ではなく、新しい治療ターゲットの確立が必要である。本研究により、ASCが膵癌の増殖に寄与していることが明らかになった。膵癌においてASCを標的とした新しい治療法の確立につながると考えられた。

Research Products

• [Journal Article] ABO Blood Type and the Long-term Outcomes of Pancreatic Cancer (2020)
  • Author(s): Tanaka Y, Kumagi T, Terao T, Kuroda T, Yokota T, Azemoto N, Imamura Y, Uesugi K, Kisaka Y, Shibata N, Koizumi M, Ohno Y, Kanemitsu K, Yukimoto A, Tange K, Nishiyama M, Miyake T, Miyata H, Ishii H, Abe M, Hiasa Y; Ehime Pancreato-Cholangiology (EPOCH) Study Group.
  • Journal Title: Internal Medicine Volume: 59 Issue: 6 Pages: 761-768
  • DOI: 10.2169/internalmedicine.3748-19
  • NAID: 130007808818
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-03-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance (2019)
  • Author(s): Kumagi T, Terao T, Yokota T, Azemoto N, Kuroda T, Imamura Y, Uesugi K, Kisaka Y, Tanaka Y, Shibata N, Koizumi M, Ohno Y, Yukimoto A, Tange K, Nishiyama M, Kanemitsu K, Miyake T, Miyata H, Ishii H, Hiasa Y; Ehime Pancreato-Cholangiology (EPOCH) Study Group.
  • Journal Title: Mayo Clinic Proceedings Volume: 94 Issue: 10 Pages: 2004-2010
  • DOI: 10.1016/j.mayocp.2018.12.034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 膵癌におけるインフラマソーム・ASCの役割 (2019)
  • Author(s): 小泉光仁，今村良樹，兼光梢，黒田太良，渡辺崇夫, 熊木天児，阿部雅則，日浅 陽一
  • Organizer: 第112回日本消化器病学会四国支部例会