Elucidation of cell death mechanisms in the colorectal cancer microenvironment and therapeutic development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08420
• 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: Osaka University
• Principal Investigator: Hayashi Yoshito 大阪大学, 医学系研究科, 助教 (80647123)
• Co-Investigator(Kenkyū-buntansha): 新崎 信一郎 大阪大学, 医学系研究科, 講師 (60546860) ; 辻井 芳樹 大阪大学, 医学系研究科, 助教 (80795170) ; 飯島 英樹 大阪大学, 医学系研究科, 特任准教授 (90444520)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 癌微小環境 / 癌関連線維芽細胞 / オートファジー / 大腸癌

Outline of Final Research Achievements

The aim of the present study was to elucidate the activation mechanism of fibroblasts, which constitute the cancer microenvironment, and to develop novel therapeutic strategies targeting cancer-associated fibroblasts to inhibit colorectal cancer progression. Using cell lines, we have elucidated the mechanism by which exosomes derived from p53-deficient cancer cells inhibit fibroblast autophagy and consequently activate fibroblasts. We also examined the expression of microRNAs in exosomes derived from cancer cells, and identified the microRNA which suppress autophagy of fibroblasts. We showed that autophagy in fibroblasts may play an important role in the mechanism of colorectal cancer progression.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

本研究により、癌微小環境を構成する癌細胞と線維芽細胞の細胞間相互作用において、癌細胞由来エクソソームがオートファジーの抑制を介して線維芽細胞を活性化することを示す学術的成果を得ることができた。本邦において大腸癌患者の増加傾向が続いているが、癌細胞由来エクソソームや線維芽細胞のオートファジーが新規治療標的となりうることを示せたことは社会的意義が高いと考える。