Novel immunocompetent murine models representing advanced local and metastatic pancreatic cancer.
BACKGROUND
The development of novel therapeutics for pancreatic cancer has been hindered by a lack of relevant preclinical models. The purpose of this study was to evaluate the clinical relevancy of two pancreatic cancer models using standard-of-care therapeutic agent gemcitabine.


METHODS
Murine Panc02 cells were injected directly into the spleen or pancreas of C57BL/6 mice to respectively create models of metastatic and locally advanced pancreatic cancer. Beginning 7 d post-Panc02 injection, treated mice received 20 mg/kg gemcitabine i.p. every 3 d. Animals were sacrificed when the untreated mice became moribund and tumor/liver weight used to assess tumor burden.


RESULTS
Untreated mice became moribund 22 d after pancreatic Panc02 injection. Gross analysis revealed localized pancreatic tumors weighing 1.063 g. Intrasplenic Panc02 injection produced extensive liver metastasis by d 15 when the untreated mice first became moribund. Liver weights at this time averaged 3.6 g compared with the average non-tumor-bearing weight of 1.23 g. Gemcitabine therapy resulted in a 54% decrease in localized pancreatic tumor weight and 62.5% decrease in metastatic liver weight. Additionally, gemcitabine therapy extended animal survival to 20.5 d compared with 18.0 d average for the untreated mice.


CONCLUSIONS
We describe two models depicting both locally advanced and metastatic pancreatic cancer in immunocompetent mice. In efforts to establish baseline therapeutic efficacy, we determined that gemcitabine reduces tumor burden in both models and enhances survival in the metastatic model. These clinically relevant models provide valuable tools to evaluate novel therapeutics in pancreatic cancer.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Elizabeth C
EC
Little
Cindy
C
Wang
Patricia M
PM
Watson
Dennis K
DK
Watson
David J
DJ
Cole
E Ramsay
ER
Camp
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D007121:Immunocompetence / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000379:methods; D010179:Pancreas / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000556:secondary*; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine