Classification and functional analysis of mesenchymal cells in pancreatic ductal adenocarcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17611
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Maehira Hiromitsu 滋賀医科大学, 医学部, 助教 (30564918)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵癌 / 癌微小環境 / 癌関連線維芽細胞

Outline of Final Research Achievements

We established 8 cancer-derived pancreatic fibroblasts (tPFB) and 3 non-cancer-derived pancreatic fibroblasts (nPFB) as cell lines, and found that the gene expression phenotypes of each were significantly different. Non-contact co-culture of tPFB and pancreatic cancer cell lines (T3M-4, MIAPaCa-2) increased gene expression of iCAF markers several hundred fold. This was the same result as when IL-1α added on tPFB. In vitro co-culture of pancreatic cancer cell lines and tPFB revealed no effect of tPFB on the proliferation of pancreatic cancer cells. However, it was found that co-transplantation of cancer cells and tPFB into nude mice in vivo showed much faster tumor growth compared to cancer alone.

Free Research Field

pancreatic cancer

Academic Significance and Societal Importance of the Research Achievements

現在盛んに研究されているCAFの不均一性の証明と一致して、表現型の異なる2種類の線維芽細胞株を樹立できたことで、CAFの表現型の違いと機能の違いについて、前臨床で解析する手段が得られた。実際に、癌由来の線維芽細胞は実際にin vivoで腫瘍増大に寄与しており、この線維芽細胞の表現型と機能の違いを解析することで、CAFの癌との相互作用を明らかにすることができる。こうしたCAFの不均一性と機能についての研究が進むことで、CAFやCAFが出す癌に対するシグナルを標的とした新たな治療戦略が登場することが予想され、膵癌の予後改善につながると考えられる。