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胰腺导管内乳头状黏液性肿瘤在鸡胚中快速异种移植并预测侵袭性。

Intraductal papillary mucinous neoplasm of the pancreas rapidly xenografts in chicken eggs and predicts aggressiveness.

机构信息

Section of Surgical Research and Molecular OncoSurgery, Heidelberg, Germany.

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

出版信息

Int J Cancer. 2018 Apr 1;142(7):1440-1452. doi: 10.1002/ijc.31160. Epub 2017 Nov 29.

Abstract

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a high risk of progressing to invasive pancreatic ductal adenocarcinoma (PDA), but experimental models for IPMN are largely missing. New experimental systems for the molecular characterization of IPMN and for personalized prognosis and treatment options for IPMN are urgently needed. We analyzed the potential use of fertilized chicken eggs for the culture of freshly resected IPMN tissue. We transplanted 49 freshly resected IPMN tissues into eggs and compared the growth characteristics to IPMN tissues transplanted into mice; this was followed by an analysis of histology, morphology, and marker expression. Of the IPMN tissues transplanted into eggs, 63% formed tumor xenografts within 4 days, while none of the 12 IPMN tissues transplanted into immunodeficient mice engrafted. In the eggs, the grafting efficiency of high-grade (n = 14) and intermediate-grade (n = 17) dysplasia was 77% and was significantly higher than the 39% grafting efficiency of low-grade dysplasia (n = 18). According to mucinous expression, 46 IPMN tissues were classified into gastric (n = 6), intestinal (n = 3), oncocytic (n = 23), and pancreatobiliary (n = 14) subtypes. The grafting efficiency was highest for the pancreatobiliary subtype (86%), followed by the oncocytic (70%), gastric (33%) and intestinal (33%) subtypes. The morphology and expression patterns of mucins, progression markers and pancreatic ductal markers were comparable between the primary IPMN tissues and their xenograft copies. The individual tumor environment was largely maintained during subtransplantation, as evaluated upon passage 6. This new IPMN model may facilitate experimental studies and treatment decisions for the optimal personalized management of IPMN.

摘要

胰腺导管内乳头状黏液性肿瘤 (IPMN) 有进展为侵袭性胰腺导管腺癌 (PDA) 的高风险,但 IPMN 的实验模型在很大程度上缺失。迫切需要用于 IPMN 的分子特征分析以及用于 IPMN 的个性化预后和治疗选择的新的实验系统。我们分析了受精鸡卵用于培养新切除的 IPMN 组织的潜力。我们将 49 个新切除的 IPMN 组织移植到鸡蛋中,并将其与移植到小鼠中的 IPMN 组织的生长特征进行比较;随后对组织学、形态和标志物表达进行了分析。在移植到鸡蛋中的 IPMN 组织中,有 63%在 4 天内形成了肿瘤异种移植物,而移植到免疫缺陷小鼠中的 12 个 IPMN 组织中没有一个形成。在鸡蛋中,高级别 (n = 14) 和中级别 (n = 17) 发育不良的移植效率为 77%,显著高于低级别发育不良 (n = 18) 的 39%的移植效率。根据黏液表达,46 个 IPMN 组织被分为胃 (n = 6)、肠 (n = 3)、嗜酸细胞 (n = 23) 和胰胆管 (n = 14) 亚型。胰胆管亚型的移植效率最高 (86%),其次是嗜酸细胞 (70%)、胃 (33%) 和肠 (33%) 亚型。在异种移植中,原发 IPMN 组织及其副本的黏液、进展标志物和胰腺导管标志物的形态和表达模式具有可比性。在第 6 次传代时评估,个体肿瘤环境在很大程度上得以维持。这种新的 IPMN 模型可能有助于实验研究和治疗决策,以实现 IPMN 的最佳个体化管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7813/5836935/4b5ef86eed9d/IJC-142-1440-g001.jpg

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