Epigenetic regulation of pancreatic cancer stroma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08324
• 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 Tokyo
• Principal Investigator: Sato Tatsuya 東京大学, 医学部附属病院, 助教 (60843753)
• Co-Investigator(Kenkyū-buntansha): 立石 敬介 東京大学, 医学部附属病院, 届出研究員 (20396948)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌

Outline of Final Research Achievements

Although it has become clear that cancer-associated fibroblast CAFs in pancreatic cancer tissue are diverse and plastic, it is not clear how their diverse profiles and mutual plasticity contribute to cancer progression. It is conceivable that these diverse CAF clusters are dynamically migratory to each other, and that epigenomic regulatory mechanisms that play an important role in cell plasticity may also be associated with the regulation of their diversity and indirectly contribute to the malignant potential of the tumors themselves.
In this study, we investigated not only the functional activation of CAFs in human pancreatic cancer, but also the effects of their diversity and mutual plasticity on the malignant potential of the tumor itself, as well as their relationship with epigenomic regulation of gene expression.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

腫瘍内の間質細胞や免疫細胞を含めた微小環境が癌細胞自体の増殖や悪性度に影響を及ぼし、例えばそれは薬剤による治療抵抗性などにも関連する。豊富な線維性間質によるDesmoplasiaをその病理学的特徴とする膵癌では、その腫瘍組織の大部分を占める活性化したCAFや免疫細胞などの間質系細胞と、産生される膠原線維や増殖因子が腫瘍促進的な微小環境を構成し、膵癌細胞自体の増殖や各種治療に対する抵抗性を誘導すると考えられてきた。本研究はその膵癌腫瘍組織の重要性におけるエピゲノム制御の関係を明らかにする学術的意義を有する。