Bailey Katie L, Cartwright Sara B, Patel Neesha S, Remmers Neeley, Lazenby Audrey J, Hollingsworth Michael A, Carlson Mark A
Department of Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
VA Medical Center, Surgery 112, 4101 Woolworth Ave, Omaha, NE, 68105, USA.
Sci Rep. 2021 Jun 28;11(1):13436. doi: 10.1038/s41598-021-92852-2.
We describe our initial studies in the development of an orthotopic, genetically defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T. The transformed cell lines outperformed the primary and SV40T immortalized cells in terms of proliferation, population doubling time, soft agar growth, transwell migration and invasion. The transformed cell line grew tumors when injected subcutaneously in nude mice, forming glandular structures and staining for epithelial markers. Future work will include implantation studies of these tumorigenic porcine pancreatic cell lines into the pancreas of allogeneic and autologous pigs. The resultant large animal model of pancreatic cancer could be utilized for preclinical research on diagnostic, interventional, and therapeutic technologies.
我们描述了我们在开发一种原位、基因定义的大型胰腺癌动物模型方面的初步研究。从家猪的胰管中分离出原代胰腺上皮细胞。用致癌性KRAS和SV40T从这些原代细胞中生成了一个转化细胞系。在增殖、群体倍增时间、软琼脂生长、Transwell迁移和侵袭方面,转化细胞系的表现优于原代细胞和SV40T永生化细胞。将该转化细胞系皮下注射到裸鼠体内时可形成肿瘤,形成腺状结构并表达上皮标志物。未来的工作将包括将这些致瘤性猪胰腺细胞系植入同种异体和自体猪的胰腺中进行研究。由此产生的大型胰腺癌动物模型可用于诊断、介入和治疗技术的临床前研究。