Mouse-Derived Allografts: A Complementary Model to the KPC Mice on Researching Pancreatic Cancer In Vivo

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers and has an extremely undesirable prognosis because little is known about the initiation and progression mechanisms of pancreatic cancer. The lack of an appropriate research model may have hindered this process. Using LSL-Kras(G12D/+); Trp53(fl/+); Pdx1-Cre (KPC) mice and the tumor tissue fragment transplantation technique, we constructed the mouse-derived subcutaneous/orthotopic allograft tumor models (MDAs-ST/OT). H&E staining, Masson staining and immunohistochemical staining were adopted to describe the histopathology and biomarkers of the MDAs and the recruitment of immune cells. The intervention of gemcitabine was applied to measure the chemotherapeutic response of MDAs tumors. MDAs could mimic the pathological histology and the high proliferation characteristics of PDAC. Indeed, the fibrosis, epithelial-mesenchyme transition (EMT) and invasion/metastasis related markers of MDAs were similar to those observed in pancreatic cancer. Further, the recruitment of immune cells in PDAC was precisely simulated by MDAs. In addition, gemcitabine suppressed the tumor growth of MDAs-ST significantly. MDAs are an effective model for investigating the progression and treatment of pancreatic cancer. (C) 2019 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.