Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Department of Surgery, Charité Universitätsmedizin Berlin, 10117, Berlin, Germany.
Lab Invest. 2020 Jul;100(7):1003-1013. doi: 10.1038/s41374-020-0372-0. Epub 2020 Jan 31.
Intraductal tubulopapillary neoplasm (ITPN) is a distinct precancerous lesion in the pancreas with unique clinical and molecular features. Although in vitro studies in two-dimensional culture have led to numerous important insights in pancreatic cancer, such models are currently lacking for precancerous lesions. In this study, we report the generation and characterization of a cell line from a human pancreatic ITPN. Neoplastic cells were initially cultured in a three-dimensional organoid system, followed by transfer to two-dimensional culture. RNA sequencing revealed a gene expression profile consistent with pancreatic ductal origin, and whole genome sequencing identified many somatic mutations (including in genes involved in DNA repair and Wnt signaling) and structural rearrangements. In vitro characterization of the tumorigenic potential demonstrated a phenotype between that of normal pancreatic ductal cells and cancer cell lines. This cell line represents a valuable resource for interrogation of unique ITPN biology, as well as precancerous pancreatic lesions more generally.
管状乳头状腔内肿瘤(ITPN)是胰腺中一种独特的癌前病变,具有独特的临床和分子特征。尽管二维培养的体外研究为胰腺癌带来了许多重要的见解,但目前缺乏针对癌前病变的此类模型。在这项研究中,我们报告了从人胰腺 ITPN 中生成和表征的细胞系。首先,将肿瘤细胞在三维类器官系统中培养,然后转移到二维培养中。RNA 测序显示出与胰腺导管起源一致的基因表达谱,全基因组测序鉴定出许多种体细胞突变(包括参与 DNA 修复和 Wnt 信号通路的基因)和结构重排。体外肿瘤发生潜能的表征显示出介于正常胰腺导管细胞和癌细胞系之间的表型。该细胞系是研究独特的 ITPN 生物学以及更普遍的癌前胰腺病变的宝贵资源。