Research on carcinogenesis and cell differentiation using established human pancreatic acinar cell carcinoma cell line

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Kita Emiri 千葉県がんセンター(研究所), 消化器内科, 医長 (20773980)
• Co-Investigator(Kenkyū-buntansha): 筆宝 義隆 千葉県がんセンター(研究所), 発がん制御研究部, 部長 (30359632)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腺房細胞癌 / オルガノイド

Outline of Final Research Achievements

Pancreatic atinar cell carcinoma is a rare type of cancer, and there are many unknowns regarding the mechanism of carcinogenesis and the efficacy of drugs. In this study, we succeeded in culturing human pancreatic acinar cell carcinoma-derived organoids and performed histological search, protein expression analysis, and genetic analysis to confirm that the characteristics of pancreatic acinar cell carcinoma were retained and to collect basic data on the disease. In addition, drug screening was conducted using cultured cells to identify bortezomib as a novel therapeutic candidate,and genetic modification enabled us to examine how cancer stem cell-associated markers are involved in the oncogenic process. These results suggest the usefulness of this cell line in the research of pancreatic acinar cell carcinoma.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

膵腺房細胞癌は膵腫瘍の中でも希少な癌種であり癌化メカニズムは未解明であった。今回オルガノイド培養法で得られた腺房細胞癌由来オルガノイドはより生体に近い3次元培養環境下で培養可能であり、なおかつ2次元培養細胞に比して増殖が速く安定しており、遺伝子変異の導入や薬剤スクリーニングなど、保存検体では難しい種々の各種解析を行える他、マウスに皮下腫瘍を形成させることでin vivoの検討も可能であることが確認された。得られた細胞は実際にボルテゾミブが有効であることを発見し、細胞の遺伝子改変により癌化メカニズムに関する検討も可能であったことから、本研究は臨床的にも学問的にも意義深いものと考えられた。