Surgical Department, University of Heidelberg, Heidelberg, Germany.
Pancreas. 2011 Mar;40(2):242-6. doi: 10.1097/MPA.0b013e3182016a08.
In the hamster model, pancreatic ductal adenocarcinoma develops after treatment with N-nitrosobis-(2-oxopropyl)amino (BOP). In this model, Langerhans islets play a central role in carcinogenesis. In contrast, treatment with BOP in rats and mice did not result in cancer development. We investigated whether pancreatic tumors develop after orthotopic implantation of hamster islets into severe combined immunodeficiency mouse pancreases and subsequent treatment with BOP. This occurrence would suggest that pancreatrophic carcinogens are metabolized by islet cells.
Twenty-four severe combined immunodeficiency mice were separated into 2 groups of 12 animals. Five hundred hamster islets were implanted in the splenic lobe of the mouse pancreases in the treatment group, whereas animals of the control group received a sham operation. All animals were treated with BOP for 5 weeks. One year later, the animals were killed and investigated for tumors.
Carcinomas developed in 3 animals in the treatment group and none in the control group. The tumors displayed the histomorphological phenotype pancreatic ductal adenocarcinoma.
Islet cells seem to play a role in pancreatic carcinogenesis in this animal model and therefore represent useful targets for future investigations on the putative role of islet cells during pancreatic ductal adenocarcinoma tumorigenesis.
在仓鼠模型中,经 N-亚硝基双(2-氧丙基)胺(BOP)处理后会发展为胰腺导管腺癌。在该模型中,胰岛在癌变过程中起着核心作用。相比之下,BOP 处理大鼠和小鼠不会导致癌症发展。我们研究了将仓鼠胰岛原位植入严重联合免疫缺陷小鼠胰腺后,再用 BOP 处理是否会导致胰腺肿瘤的形成。如果发生这种情况,则表明胰岛细胞代谢了胰腺促癌剂。
将 24 只严重联合免疫缺陷小鼠分为两组,每组 12 只。实验组将 500 个仓鼠胰岛植入小鼠胰腺的脾叶,而对照组接受假手术。所有动物均用 BOP 处理 5 周。一年后,处死动物并检查肿瘤。
实验组的 3 只动物发生了癌,对照组则没有。肿瘤表现出胰腺导管腺癌的组织形态表型。
在该动物模型中,胰岛细胞似乎在胰腺癌变过程中起作用,因此是未来研究胰岛细胞在胰腺导管腺癌肿瘤发生过程中潜在作用的有用靶点。