Discovery of pancreatic cancer microenvironments by gene expression mapping and metabolome mapping.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17622
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: TORATA Nobuhiro 九州大学, 大学病院, 臨床検査技師 (00398075)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 遺伝子発現マッピング / メタボロミクスマッピング

Outline of Final Research Achievements

To discover of pancreatic cancer microenvironments, correlation between amount of cancer associated fibroblasts(CAF) and pancreatic cancer cell differentiation are analyzed. Positive correlation between cancer cell differentiation and amount of CAF, in which has a potential of cancer cells proliferation, is detected by using human pancreatic cancer organoid assay. Positive correlation between cancer cell differentiation and expression of cholesterol synthesis related genes, especially mevalonate pathway, is also detected by comprehensive gene expression analysis. Additionally, well differentiate pancreatic organoid indicated significant growth suppression by medication of simvastatin which is an inhibitor of HMG-CoA reductase in comparison with poorly differentiated one.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

膵癌は癌の中でもっとも予後不良な癌の一つで、その特徴の一つにdesmoplasiaと呼ばれる豊富な間質増生があり、治療抵抗性や、薬剤送達率低下への関与が明らかにされている。本研究成果は、細胞の相互作用を再現したヒト膵癌オルガノイドを用い、腫瘍微小環境における、腫瘍分化度と癌間質量の関連性を明らかにするだけでなく、cholesterol synthesis関連遺伝子の発現が増加していることを明らかにし、治療ターゲットとしての可能性を見出した点で学術的、社会的意義が高い。