Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adv Exp Med Biol. 2019;1164:3-10. doi: 10.1007/978-3-030-22254-3_1.
Pancreatic ductal adenocarcinoma is an overwhelming fatal disease that often presents with overt metastases and ultimately causes the majority of cancer-associated deaths. The mechanisms underlying the metastatic cascade are complex, and research in recent years has begun to provide insights into the underlying drivers of this phenomenon. It has become clear that cancer cells, in particular pancreatic cancer cells, possess properties of plasticity involving bidirectional transition between epithelial and mesenchymal identities. Furthermore, recent work has begun to establish that there are distinct hybrid states between purely epithelial and purely mesenchymal states that cancer cells may reside, in order to thrive at different stages of carcinogenesis. We discuss how this plasticity is important for different phases of the metastatic cascade, from delamination to colonization, and how different epithelial-mesenchymal states may affect metastatic organotropism. In this review, we summarize the current understanding of pancreatic cancer cell plasticity and metastasis, and highlight current model systems that can be used to study these phenomena.
胰腺导管腺癌是一种致命性极强的疾病，常伴有明显的转移，最终导致大多数癌症相关的死亡。转移级联的机制很复杂，近年来的研究开始为这一现象的潜在驱动因素提供了一些见解。已经很清楚的是，癌细胞，特别是胰腺癌细胞，具有可塑性，涉及上皮和间充质特征之间的双向转化。此外，最近的工作开始证实，在纯粹的上皮和纯粹的间充质状态之间存在着明显的混合状态，癌细胞可能存在于这些状态中，以在癌变的不同阶段茁壮成长。我们讨论了这种可塑性对于转移级联的不同阶段（从脱层到定植）的重要性，以及不同的上皮-间充质状态如何影响转移的器官趋向性。在这篇综述中，我们总结了目前对胰腺癌细胞可塑性和转移的理解，并强调了目前可用于研究这些现象的模型系统。
