A novel, clinically relevant animal model of metastatic pancreatic adenocarcinoma biology and therapy

In this study, we report a metastatic model of Panc02 murine pancreatic ade nocarcinoma. Parental Panc02 cells were orthotopically implanted into the p ancreas of syngeneic C57BL/6 mice. Tumor cells were isolated from liver mic rometastases 90 d after tumor implantation and established as a culture (Pa nc02-H1). The Panc02-H1 cells were then implanted into the pancreas of mice . Liver metastases were then collected and established as Panc02-H2 cells. This process was repeated until the Panc02-H7 cell line was established. Th ese cells were extremely aggressive after implantation as manifested by pro gressive growth in the pancreas, peritoneal dissemination, and distant meta stasis to multiple organs, including the liver and lungs. Moreover, Panc02- H7 cells expressed the inducible nitric oxide synthase gene at a very low l evel in culture and produced highly vascularized tumors having a large numb er of infiltrating macrophages. Collectively, this model system should be a valuable tool for investigating the molecular mechanisms governing pancrea tic cancer growth and metastasis and exploring potential treatment modaliti es for this disease.