2022 Fiscal Year Final Research Report
The use of 3D cell culture to study the mechanisms underlying aberrant ECM remodeling in pancreatic cancer stroma
Project/Area Number |
20K16989
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 膵がん / 細胞外基質 / 線維化 / 立体培養法 / 線維芽細胞 / 薬物送達 / 間質 / 細胞外基質リモデリング |
Outline of Final Research Achievements |
Fibrosis, a histopathological hallmark of pancreatic cancer, constitutes a barrier to drug delivery. The present research project was aimed at elucidating the mechanisms governing the generation of fibrotic barriers in pancreatic cancer to better inform the development of therapeutic strategies to overcome these barriers. The project focused on the abnormal orientation of fibroblasts and extracellular matrix (ECM) components in the fibrotic stroma of pancreatic cancer. In the project, a novel 3D in vitro model of the fibrotic pancreatic cancer stroma was successfully established. Through analyses of these models, the molecular mechanisms responsible for the abnormal orientation of fibroblasts/ECM were dissected. Furthermore, these pathways were found to be promising targets in augmenting drug delivery through fibrotic barriers.
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Free Research Field |
病態生理学
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Academic Significance and Societal Importance of the Research Achievements |
膵がんの5年生存率は約10%前後であり、他の悪性腫瘍と比べても予後が極めて悪い。早期発見が困難なのも一因であるが、膵がんは各モダリティの治療法に対し高い抵抗性を示す。膵がんの治療抵抗性獲得に、線維化が密接に関わるが、その治療的制御法は未確立である。本研究はこうした状況を打開すべく、線維化の特徴である「異常配向」に着目した解析を立体培養モデルにおいて実施し、異常配向獲得を司る分子メカニズムを解析し、さらにその標的化による薬物送達効率改善の可能性を示した。今後の動物モデル等における治療効果の検証実験を通じ、線維化制御を通じた膵がんの新規治療戦略の確立に資する知見を得た点に本研究の意義がある。
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