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Fibroblast subtypes in pancreatic cancer and pancreatitis: from mechanisms to therapeutic strategies

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Abstract

Excessive fibrosis is a predominant feature of pancreatic stroma and plays a crucial role in the development and progression of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Emerging evidence showed diversity and heterogeneity of fibroblasts play crucial and somewhat contradictory roles, the interactions between fibroblasts and pancreatic cells or infiltrating immune cells are of great importance during PDAC and CP progression, with some promising therapeutic strategies being tested. Therefore, in this review, we describe the classification of fibroblasts and their functions in PDAC and pancreatitis, the mechanisms by which fibroblasts mediate the development and progression of PDAC and CP through direct or indirect interaction between fibroblast and pancreatic parenchymal cells, or by remodeling the pancreatic immune microenvironment mediates the development and progression of PDAC and CP. Finally, we summarized the current therapeutic strategies and agents that directly target subtypes of fibroblasts or interfere with their essential functions.

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Funding

This work is supported by National Natural Science Foundation of China (82122010 and 82070659 to Li Wen), Shanghai Natural Science Foundation (22ZR1480500 to Li Wen), National High Level Hospital Clinical Research Funding (2022-PUMCH-E-003 to Li Wen) and CAMS Innovation Fund for Medical Sciences (2023-I2M-3-001 to Li Wen and 2022-I2M-1-004).

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Author notes

  1. Huizhen Huang and Wanyi Lu are co-first authors.

Authors and Affiliations

  1. Department of Gastroenterology, Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Nanjing Medical University, Shanghai, China

    Huizhen Huang

  2. Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China

    Wanyi Lu, Xiuli Zhang, Jiachun Pan & Li Wen

  3. State Key Laboratory of Complex, Severe, and Rare Diseases, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China

    Wanyi Lu, Xiuli Zhang, Jiachun Pan & Li Wen

  4. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China

    Feng Cao

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  3. Xiuli Zhang
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  4. Jiachun Pan
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  5. Feng Cao
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  6. Li Wen
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Contributions

LW designed and supervised the study, drafted and revised the manuscript and obtained the funding. HH performed the literature search and critical assessment of the published papers, drafted the manuscript. HH, WL and XZ drew the diagrams. XZ, WL, JP and FC revised the manuscript and participated in the intellectual discussions.

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Correspondence to Feng Cao or Li Wen.

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Huang, H., Lu, W., Zhang, X. et al. Fibroblast subtypes in pancreatic cancer and pancreatitis: from mechanisms to therapeutic strategies. Cell Oncol. (2023). https://doi.org/10.1007/s13402-023-00874-x

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