Abstracts
2000 Digestive Disease Week

# 2295 A Real-Time Fluorescent Model of Human Pancreatic Cancer Growth, Progression, and Metastases in the Nude Mouse.
Michael Bouvet, Stephanie Nardin, Meng Yang, Xiaoen Wang, Ping Giang, A. R. Moossa, Robert M. Hoffman, San Diego, CA

To understand the metastatic pattern of pancreatic cancer, we developed stable high-expression green fluorescent protein (GFP) transductants of human pancreatic cancer cell lines MiaPaCa-2 (MiaPaCa-2-GFP) and BxPC- 3 (BxPC-3-GFP). MiaPaCa-2 and BxPC-3 were transduced with the pLEIN retroviral expression vector containing the enhanced GFP and the neomycin (G418) resistance genes. Stable high GFP-expressing clones were selected in vitro. Stable high-level expression of GFP was maintained in subcutaneous- growing tumors formed after injecting MiaPaCa-2-GFP and BxPC- 3-GFP cells in nude mice. To use MiaPaCa-2-GFP and BxPC-3-GFP for visualization of metastasis, fragments of subcutaneous-growing tumors were implanted by surgical orthotopic implantation in the pancreas of nude mice or by portal vein injection of cell suspension. Subsequent micrometastases were visualized by GFP fluorescence in the peritoneum, periportal lymph nodes, liver, and lung as well as other sites in the abdominal cavity. The use of GFP-expressing MiaPaCa-2 and BxPC-3 cells transplanted by surgical orthotopic implantation or by portal vein injection revealed the extensive metastatic potential of pancreatic cancer. Furthermore, the primary tumor and subsequent metastasis were visualized by whole body imaging through the skin of the nude mouse without the need for laparotomy. Such visualization can be a practical and convenient way to follow metastasis on a real-time fashion. These new metastatic models can play a critical role in the study of the mechanism of metastasis in pancreatic cancer and in screening of therapeutics that prevent or reverse this process.