An orthotopic in vivo model of human pancreatic cancer

R. E. Schwarz, T. M. McCarty, E. A. Peralta, D. J. Diamond, J. D I Ellenhorn

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Background. Pancreatic cancer is a highly lethal disease that frequently presents in advanced stages. For most patients, treatment with great clinical efficacy does not exist. Relevant in vivo models to test novel therapies are highly desirable. Methods. The human pancreatic ductal adenocarcinoma cell line Panc-1 was injected intraperitoneally into SCID mice. The pattern of the resulting peripancreatic 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 nodules, peripancreatic and portal adenopathy developed, causing biliary obstruction. All tumor-bearing animals died of disease within 5 to 12 weeks. Survival after gemcitabine treatment and after p53-CTL injection was significantly prolonged, with some animals remaining tumor-free. Doxorubicin treatment did not yield extended survival, but led to significant toxicity. Conclusion. Intraperitoneal injection of Panc-1 cells into SCID mice produces a quasi-orthotopic tumor development model that shares many characteristics with human pancreatic cancer. The ease of cell injection, avoidance of cumbersome surgical intervention with its resulting mortality, and the reliable development of obstructive jaundice as a dependent comorbid factor render 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 predict the in vivo response, highlighting the preclinical experimental value of this model.

Original languageEnglish (US)
Pages (from-to)562-567
Number of pages6
JournalSurgery
Volume126
Issue number3
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Surgery

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    Schwarz, R. E., McCarty, T. M., Peralta, E. A., Diamond, D. J., & Ellenhorn, J. D. I. (1999). An orthotopic in vivo model of human pancreatic cancer. Surgery, 126(3), 562-567. https://doi.org/10.1016/S0039-6060(99)70099-1