Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models

Pancreatic cancer is a highly metastatic disease that responds poorly to cu rrently-available treatment. In order to better visualize and understand th e chronology and specificity of metastatic targeting of pancreatic cancer, two human pancreatic cancer cell lines, expressing green fluorescent protei n (GFP), were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tu mor fragments were transplanted by surgical orthotopic implantation (SOI) t o the nude mouse pancreas for fluorescence visualization of the chronology of pancreatic tumor growth and metastatic targeting. BxPC-3-GFP tumors deve loped rapidly in the pancreas and spread regionally to the spleen and retro peritoneum as early as six weeks. Distant metastases in BxPC-3-GFP were rar e. In contrast, MIA-PaCa-2-GFP grew more slowly in the pancreas but rapidly metastasized to distant sites including liver and portal lymph nodes. Regi onal metastases in MIA-PaCa-2-GFP were rare. These studies demonstrate that pancreatic cancers have highly specific and individual 'seed-soil' interac tions governing the chronology and sites of metastatic targeting.