Ovarian Cancer Research Center, Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, United States; Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, United States.
Methods Cell Biol. 2022;168:139-159. doi: 10.1016/bs.mcb.2021.12.013. Epub 2022 Jan 21.
Chronic inflammation is known to be associated with pancreatic cancer, however a complete picture regarding how these pathologies intersect is still being characterized. In vivo model systems are critical for the study of mechanisms underlying how inflammation accelerates neoplasia. Repeat injection of cerulein, a cholecystokinin (CCK) analog, is widely used to experimentally induce acute and chronic pancreatitis in vivo. Chronic cerulein administration into genetically engineered mouse models (GEMMs) with predisposition to pancreatic cancer can induce a pro-inflammatory immune response, pancreatic acinar cell damage, pancreatic stellate cell activation, and accelerate the onset of neoplasia. Here we provide a detailed protocol and insights into using cerulein to induce pancreatitis in GEMMs, and methods to experimentally assess inflammation and pancreatic neoplasia.
慢性炎症与胰腺癌有关,然而,关于这些病理学如何交叉的全貌仍在描述中。体内模型系统对于研究炎症如何加速肿瘤发生的机制至关重要。重复注射鹅去氧胆酸(一种胆囊收缩素(CCK)类似物)广泛用于在体内实验性诱导急性和慢性胰腺炎。在具有胰腺癌易感性的基因工程小鼠模型(GEMM)中,慢性鹅去氧胆酸给药可诱导促炎免疫反应、胰腺腺泡细胞损伤、胰腺星状细胞激活,并加速肿瘤的发生。在这里,我们提供了一个详细的方案,并深入了解使用鹅去氧胆酸在 GEMM 中诱导胰腺炎的方法,以及实验评估炎症和胰腺肿瘤发生的方法。