Ductal vs. acinar? Recent insights into identifying cell lineage of pancreatic ductal adenocarcinoma.
Ductal vs. acinar? Recent insights into identifying cell lineage of pancreatic ductal adenocarcinoma.
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DOI：
10.21037/apc.2019.06.03
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发表时间：
2019-06-01
期刊：
影响因子：
--
通讯作者：
Wang, Pei
中科院分区：
文献类型：
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作者：
Xu, Yi;Liu, Jun;Wang, Pei
胰腺导管腺癌（PDAC）是一种致命的疾病，5年生存率低于8%。迄今为止，没有早期检测方法或有效的治疗方法。关于PDAC的发病机制仍有许多问题有待解决，其中关于PDAC的细胞谱系的争论更值得关注。由于大多数PDAC病例的导管形态，导管细胞最初被认为是PDAC的起源细胞。然而，最近的研究表明，腺泡细胞对KRAS突变更敏感，并且倾向于有效地发展为PanIN和PDAC，很可能是通过经历腺泡到导管化生进入有助于PDAC启动的短暂状态。还有证据表明，当暴露于某些遗传环境和刺激时，导管和腺泡细胞都可能发展为PDAC，这表明需要更多的审查来鉴定PDAC个体病例的真实细胞谱系。在这项工作中，我们总结了最近的研究结果，在确定PDAC的细胞起源，推进我们的知识的开始和疾病的进展的目标。我们还讨论了各种模型和技术，调查早期事件的PDAC。更好地了解这些细胞事件对于确定早期诊断和治疗PDAC的新方法至关重要。
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of less than 8%. To date, there are no early detection methods or effective treatments available. Many questions remain to be answered in regards to the pathogenesis of PDAC, among which, the controversy over the cell lineage of PDAC demands more attention. Ductal cells were originally thought to be the cell of origin for PDAC due to the ductal morphology of most cases of PDAC. However, recent studies have demonstrated that acinar cells are more sensitive to KRAS mutation and tend to develop to PanIN and PDAC effectively, very likely by undergoing acinar to ductal metaplasia into a transient state that contributes to PDAC initiation. There is also evidence that both ductal and acinar cells can potentially develop to PDAC when exposed to certain genetic settings and stimuli, suggesting that more scrutiny is required for the identification of the true cell lineage of individual cases of PDAC. In this work, we summarize recent findings in the identification of the cellular origin of PDAC, with the goal of advancing our knowledge on the initiation and progression of the disease. We also discuss various models and techniques for investigating early events of PDAC. Better understanding of these cellular events is crucial to identify new methods for the early diagnosis and treatment of PDAC.