Organotypic Culture of Acinar Cells for the Study of Pancreatic Cancer Initiation.
Organotypic Culture of Acinar Cells for the Study of Pancreatic Cancer Initiation.
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DOI：
10.3390/cancers12092606
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发表时间：
2020-09-12
期刊：
影响因子：
5.2
通讯作者：
Carrer A
中科院分区：
文献类型：
--
作者：
Paoli C;Carrer A
胰腺癌是一种致命的疾病，预后很差。更好地了解导致胰腺上皮细胞恶性转化的分子变化对于降低疾病发生率和及早发现疾病至关重要，因为这种疾病可以通过手术切除。胰腺癌前病变细胞的培养在技术上具有挑战性，但却是研究肿瘤进化和早期致癌改变的重要工具。在这里，我们将从技术和历史的角度描述胰腺腺泡细胞的分离及其在肿瘤起始研究中的价值。胰腺导管腺癌(PDA)的癌变是一个多步骤发展的过程，由此疾病获得了越来越多的侵袭性病理特征。另一方面，对疾病初始阶段的调查很少。解码导致致癌转化的一系列事件对于设计早期诊断策略以及应对肿瘤发病至关重要。谱系追踪实验表明，胰腺癌病变起源于腺泡细胞，这是胰腺上皮中一种高度特化的细胞类型。原代腺泡细胞可以在体外以类器官样三维球体的形式存活，在不同的细胞和非细胞自主刺激下，可以转分化为具有清晰导管形态的细胞。这一事件被称为腺泡-导管化生，概括了疾病发生的组织学和分子特征。在这里，我们将讨论原代胰腺腺泡细胞的分离和培养，提供一个历史和技术的视角。胰腺癌研究的影响也将被辩论。特别是，我们将剖析转录、表观遗传和代谢重编程在肿瘤启动中的作用，我们将展示如何使用体外腺泡细胞培养来模拟这一过程。最后，我们将对利用器官培养描述的PDA启动机制进行综述。
Pancreatic Cancer is a deadly disease, with a dismal prognosis. A better understanding of the molecular alterations that cause the malignant transformation of pancreatic epithelial cells is pivotal to curtail disease incidence and detect the disease early when it can be surgically resected. The culture of pancreatic pre-malignant cells is technically challenging, but a great tool for the study of tumor evolution and early oncogenic alterations. Here, we will describe the isolation of pancreatic acinar cells and its value for the study of tumor initiation, from a technical and historical perspective. The carcinogenesis of pancreatic ductal adenocarcinoma (PDA) progresses according to multi-step evolution, whereby the disease acquires increasingly aggressive pathological features. On the other hand, disease inception is poorly investigated. Decoding the cascade of events that leads to oncogenic transformation is crucial to design strategies for early diagnosis as well as to tackle tumor onset. Lineage-tracing experiments demonstrated that pancreatic cancerous lesions originate from acinar cells, a highly specialized cell type in the pancreatic epithelium. Primary acinar cells can survive in vitro as organoid-like 3D spheroids, which can transdifferentiate into cells with a clear ductal morphology in response to different cell- and non-cell-autonomous stimuli. This event, termed acinar-to-ductal metaplasia, recapitulates the histological and molecular features of disease initiation. Here, we will discuss the isolation and culture of primary pancreatic acinar cells, providing a historical and technical perspective. The impact of pancreatic cancer research will also be debated. In particular, we will dissect the roles of transcriptional, epigenetic, and metabolic reprogramming for tumor initiation and we will show how that can be modeled using ex vivo acinar cell cultures. Finally, mechanisms of PDA initiation described using organotypical cultures will be reviewed.
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影响因子：
7.3
作者：
Cleveland, Megan H.;Sawyer, Jacob M.;Afelik, Solomon;Jensen, Jan;Leach, Steven D.
通讯作者：
Leach, Steven D.
影响因子：
28.2
作者：
Carrer, Alessandro;Trefely, Sophie;Wellen, Kathryn E.
通讯作者：
Wellen, Kathryn E.
使用逆行病毒载体递送和体内 CRISPR/Cas9 介导的体细胞基因组编辑进行胰腺癌建模。
影响因子：
10.5
作者：
Chiou SH;Winters IP;Wang J;Naranjo S;Dudgeon C;Tamburini FB;Brady JJ;Yang D;Grüner BM;Chuang CH;Caswell DR;Zeng H;Chu P;Kim GE;Carpizo DR;Kim SK;Winslow MM
通讯作者：
Winslow MM
影响因子：
--
作者：
Benitz S;Regel I;Reinhard T;Popp A;Schäffer I;Raulefs S;Kong B;Esposito I;Michalski CW;Kleeff J
通讯作者：
Kleeff J
影响因子：
50.3
作者：
Fukuda A;Wang SC;Morris JP 4th;Folias AE;Liou A;Kim GE;Akira S;Boucher KM;Firpo MA;Mulvihill SJ;Hebrok M
通讯作者：
Hebrok M