2020年8月
Heterotypic 3D pancreatic cancer model with tunable proportion of fibrotic elements
Biomaterials
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- 巻
- 251
- 号
- 開始ページ
- 120077
- 終了ページ
- 120077
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.biomaterials.2020.120077
Pancreatic ductal adenocarcinoma (PDAC) is an often lethal disease characterized by a dense, fibrotic stroma. However, the lack of relevant preclinical models that recapitulate the characteristic histopathology of human PDAC in vitro impedes the development of novel therapies. The amount of stromal elements differ largely within and between patients, but in vitro models of human PDAC often do not account for this heterogeneity. Indeed, analyses of human PDAC histopathology revealed that the proportion of stroma ranged from 40 to 80% across patients. We, therefore, generated a novel 3D model of human PDAC, consisting of co-cultured human PDAC tumor cells and fibroblasts/pancreatic stellate cells, in which the proportion of fibrotic elements can be tuned across the clinically observed range. Using this model, we analyzed the signaling pathways involved in the differentiation of myofibroblasts, a characteristic subpopulation of fibroblasts seen in PDAC. We show that both YAP and SMAD2/3 in fibroblasts are required for myofibroblastic differentiation and that both shared and distinct signaling pathways regulate the nuclear localization of these factors during this process. Our novel model will be useful in promoting the understanding of the complex mechanisms by which the fibrotic stroma develops and how it might be therapeutically targeted.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.biomaterials.2020.120077
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/32388166
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85084171260&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85084171260&origin=inward
- ID情報
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- DOI : 10.1016/j.biomaterials.2020.120077
- ISSN : 0142-9612
- eISSN : 1878-5905
- PubMed ID : 32388166
- SCOPUS ID : 85084171260