Li Xiaojia, He Jie, Xie Keping
Center for Pancreatic Cancer Research, The South China University of Technology School of Medicine, Guangzhou, 510006, China.
Department of Pathology, The South China University of Technology School of Medicine, Guangzhou, China.
Cell Oncol (Dordr). 2022 Apr;45(2):201-225. doi: 10.1007/s13402-022-00664-x. Epub 2022 Mar 15.
Pancreatic ductal metaplasia (PDM) is the transformation of potentially various types of cells in the pancreas into ductal or ductal-like cells, which eventually replace the existing differentiated somatic cell type(s). PDM is usually triggered by and manifests its ability to adapt to environmental stimuli and genetic insults. The development of PDM to atypical hyperplasia or dysplasia is an important risk factor for pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDA). Recent studies using genetically engineered mouse models, cell lineage tracing, single-cell sequencing and others have unraveled novel cellular and molecular insights in PDM formation and evolution. Those novel findings help better understand the cellular origins and functional significance of PDM and its regulation at cellular and molecular levels. Given that PDM represents the earliest pathological changes in PDA initiation and development, translational studies are beginning to define PDM-associated cell and molecular biomarkers that can be used to screen and detect early PDA and to enable its effective intervention, thereby truly and significantly reducing the dreadful mortality rate of PDA. This review will describe recent advances in the understanding of PDM biology with a focus on its underlying cellular and molecular mechanisms, and in biomarker discovery with clinical implications for the management of pancreatic regeneration and tumorigenesis.
胰腺导管化生（PDM）是胰腺中潜在的多种类型细胞向导管或导管样细胞的转变，这些细胞最终取代现有的分化体细胞类型。PDM通常由环境刺激和基因损伤引发，并表现出其适应这些刺激的能力。PDM发展为非典型增生或发育异常是胰腺上皮内瘤变（PanIN）和胰腺导管腺癌（PDA）的重要危险因素。最近使用基因工程小鼠模型、细胞谱系追踪、单细胞测序等方法的研究揭示了PDM形成和演变过程中全新的细胞和分子见解。这些新发现有助于更好地理解PDM的细胞起源、功能意义及其在细胞和分子水平上的调控。鉴于PDM代表了PDA起始和发展过程中最早的病理变化，转化医学研究开始确定与PDM相关的细胞和分子生物标志物，这些标志物可用于筛查和检测早期PDA，并实现其有效干预，从而真正且显著降低PDA可怕的死亡率。本综述将描述在理解PDM生物学方面的最新进展，重点关注其潜在的细胞和分子机制，以及在生物标志物发现方面的进展及其对胰腺再生和肿瘤发生管理的临床意义。
