pancreatic cancer progression by cancer-associated adipocytes derived exosome

• Project/Area Number: 19K08445
• 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: The University of Tokushima
• Principal Investigator: SATO Yasushi 徳島大学, 大学院医歯薬学研究部(医学域), 特任教授 (80343383)
• Co-Investigator(Kenkyū-buntansha): 三好 人正 徳島大学, 病院, 診療支援医師 (00814625) ; 高山 哲治 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10284994) ; 岡本 耕一 徳島大学, 病院, 講師 (60531374)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 膵臓癌 / 膵癌 / exosome / miRNA / 脂肪細胞 / 癌関連脂肪細胞

Outline of Research at the Start

膵癌は脂肪組織に囲まれていることから、その悪性化に脂肪細胞が分泌するmiRNAが膵癌の制御に重要な役割を果たす可能性が考えられる。そこで、癌関連脂肪細胞(CAA)の上清中に分泌された細胞間・臓器間のコミュニケーションを担うexosomeに着目し、これが含有するmiRNAの膵癌悪性化に関わる役割を検討する。

Outline of Final Research Achievements

We have previously reported that cancer-associated adipocytes (CAAs) play an important role in the malignant transformation of pancreatic cancer cells by enhancing their SAA-1 expression. However, the detailed mechanism has not been fully elucidated. In this study, we focused on miRNAs that specifically regulate the expression of various cancer-related genes and investigated the mechanism of CAA-induced pancreatic cancer progression by bioinformatics analysis of miRNAs contained in exosomes secreted from CAA. The results revealed that miRs produced from CAAs are introduced into pancreatic cancer cells via the exosome and suppress SOCS7 expression, thereby up regulating SAA-1 expression and promoting malignant transformation of pancreatic cancer cells. These results suggest that miR may be a candidate for novel biomarkers and molecular-targeted drugs for pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

本研究によりexosome中のmiRNAプロファイルを明らかにできればliquid biopsyによる膵癌特異的な診断モダリテイーやCAA側を標的とした全く新規の膵癌治療法の開発を行うための研究基盤が得られ、極めて難治である膵癌の診断、治療に大きな革新をもたらすことが期待でき、その臨床的意義は極めて大きいと考えられる。

Research Products

• [Journal Article] Cancer‐associated adipocytes promote pancreatic cancer progression through SAA1 expression (2020)
  • Author(s): Takehara Masanori、Sato Yasushi、Kimura Tetsuo、Noda Kazuyoshi、Miyamoto Hiroshi、Fujino Yasuteru、Miyoshi Jinsei、Nakamura Fumika、Wada Hironori、Bando Yoshimi、Ikemoto Tetsuya、Shimada Mitsuo、Muguruma Naoki、Takayama Tetsuji
  • Journal Title: Cancer Science Volume: 111 Issue: 8 Pages: 2883-2894
  • DOI: 10.1111/cas.14527
  • Peer Reviewed / Open Access
• [Presentation] 癌関連脂肪細胞に由来するエクソソーム内miRNAを介した膵癌進展機構の検討 (2021)
  • Author(s): 野田 和克, 佐藤 康史, 高山 哲治
  • Organizer: JDDW2021(第29回日本消化器医関連学会週間)
• [Presentation] 癌関連脂肪細胞の分泌型exosome内miRNAによる新たな膵癌進展機序の検討 (2021)
  • Author(s): 野田 和克, 佐藤 康史, 高山 哲治
  • Organizer: G-PLUS