Acinar cell plasticity and development of pancreatic ductal adenocarcinoma.

Acinar cell plasticity and development of pancreatic ductal adenocarcinoma.
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DOI:
10.1038/nrgastro.2017.12
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发表时间:
2017-05
期刊:
Nature reviews. Gastroenterology & hepatology
影响因子:
--
通讯作者:
Storz P
Storz P
中科院分区:
其他
文献类型:
--
作者:
Storz P

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成人胰腺的腺泡细胞表现出高度的可塑性,可以转分化为具有导管特征的祖细胞样细胞类型。这一过程被称为腺泡-导管化生(ADM),是促进胰腺损伤后再生的重要特征。来自动物模型的数据表明,对致癌信号做出反应而进行ADM的细胞是胰腺上皮内瘤变病变的先兆,可进一步发展为胰腺导管腺癌(PDAC)。由于人胰腺癌通常在转移性疾病阶段被诊断出来,了解导致其发生的过程对于发现早期检测的标志物以及实现早期干预的选择非常重要。在这里,我们讨论了腺泡细胞可塑性的关键决定因素,以及驱动腺泡细胞化生的细胞内和细胞外信号事件及其对PDAC发展的贡献。
Acinar cells in the adult pancreas show high plasticity and can undergo transdifferentiation to a progenitor-like cell type with ductal characteristics. This process, termed acinar-to-ductal metaplasia (ADM), is an important feature facilitating pancreas regeneration after injury. Data from animal models show that cells that undergo ADM in response to oncogenic signalling are precursors for pancreatic intraepithelial neoplasia lesions, which can further progress to pancreatic ductal adenocarcinoma (PDAC). As human pancreatic adenocarcinoma is often diagnosed at a stage of metastatic disease, understanding the processes that lead to its initiation is important for the discovery of markers for early detection, as well as options that enable an early intervention. Here, the critical determinants of acinar cell plasticity are discussed, in addition to the intracellular and extracellular signalling events that drive acinar cell metaplasia and their contribution to development of PDAC.
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