An orthotopic in vivo model of human pancreatic cancer

Background. Pancreatic cancer is a highly lethal disease that frequently pr esents in advanced stages. For most patients, treatment with great clinical efficacy does not exist. Relevant in vivo models to test novel therapies a re highly desirable. Methods. The human pancreatic ductal adenocarcinoma cell line Panc-1 was in jected intraperitoneally into SCID mice. The pattern of the resulting perip ancreatic as well as metastatic disease was examined. Survival experiments after chemotherapy with gemcitabine or doxorubicin, and after immunotherapy with p53-specific cytotoxic T lymphocytes were performed. Results, All animals developed isolated pancreatic tumor implants within 48 hours after injection. After the formation of invasive pancreatic tumor no dules, peripancreatic and portal adenopathy developed, causing biliary obst ruction. All tumor-bearing animals died of disease within 5 to 12 weeks. Su rvival after gemcitabine treatment and after p53-CTL injection was signific antly prolonged, with some animals remaining tumor-free. Doxorubicin treatm ent did not yield extended survival, but led to significant toxicity. Conclusion, Intraperitoneal injection of Panc-1 cells into SCID mice produc es a quasi-orthotopic tumor development model that shares many characterist ics with human pancreatic cancer. The ease of cell injection, avoidance of cumbersome surgical intervention with its resulting mortality, and the reli able development of obstructive jaundice as a dependent comorbid factor ren der this a useful model for in vivo testing of novel therapeutic approaches to pancreatic cancer. Our initial therapeutic studies demonstrate that in vitro antitumor efficacy against Panc-1 cancer cells does not necessarily p redict the in vivo response, highlighting the preclinical experimental valu e of this model.