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

Abstract

In this study, we report a metastatic model of Panc02 murine pancreatic adenocarcinoma. Parental Panc02 cells were orthotopically implanted into the pancreas of syngeneic C57BL/6 mice. Tumor cells were isolated from liver micrometastases 90 d after tumor implantation and established as a culture (Panc02-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. These cells were extremely aggressive after implantation as manifested by progressive growth in the pancreas, peritoneal dissemination, and distant metastasis to multiple organs, including the liver and lungs. Moreover, Panc02-H7 cells expressed the inducible nitric oxide synthase gene at a very low level in culture and produced highly vascularized tumors having a large number of infiltrating macrophages. Collectively, this model system should be a valuable tool for investigating the molecular mechanisms governing pancreatic cancer growth and metastasis and exploring potential treatment modalities for this disease.