An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relev ant animal models. The aims of this study were to establish an orthotopic m odel of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distan t metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm(3)) of the resulting s.c. tumors were microsurgica lly implanted into the pancreas of recipient rats. In another series of ani mals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm(3)), more local infiltration and systemic sprea d (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethalit y (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm(3)/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm(3)/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal t umors, surrounded by dense stroma, Intraperitoneal tumor dissemination in t he INJ group occurred simultaneous with primary tumor growth, indicating Pa Ca cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of du ctal pancreatic adenocarcinoma in immunocompetent rodents for preclinical t reatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.