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.
Keywords: ADM, Acinar to ductal metaplasia (ADM); CAFs, Cancer-associated fibroblasts; EMT, Epithelial-mesenchyme transition; GEMMs, Genetically engineered mouse models; Gemcitabine; KC, LSL-KrasG12D/+, Pdx1-Cre; KPC, LSL-KrasG12D/+, Trp53fl/+, Pdx1-Cre; MDAs, Mouse-derived allografts; MDAs-OT, Mouse-derived orthotopic allograft tumor models; MDAs-ST, Mouse-derived subcutaneous allograft tumor models; MDSCs, Myeloid-derived suppressor cells; Mouse-derived allografts; PDAC, Pancreatic ductal adenocarcinoma; PDXs, Patient-derived xenografts; PanINs, Pancreatic intraepithelial neoplasias; Pancreatic ductal adenocarcinoma; Tregs, T regulatory cells; Tumor tissue fragment.