Natural history of pancreatic cancer recurrence following "curative" resection in athymic mice

J Surg Res. 2008 Sep;149(1):57-61. doi: 10.1016/j.jss.2007.08.024. Epub 2007 Sep 18.

Abstract

Objective: We present a mouse model of pancreatic cancer recurrence following "curative" resection using a novel technique of implanting red fluorescent protein transfected tumor cells within a hyaluronan-based synthetic extracellular matrix into the distal pancreas of nude mice. Following "curative" pancreatic resection, we demonstrate postoperative disease recurrence by fluorescence imaging.

Methods: Forty athymic nude mice underwent pancreatic injection with red fluorescent protein transfected MiaPaCa-2 or AsPc-1 cells suspended in a synthetic extracellular matrix. In 20 animals, the distal pancreas and primary tumor were resected at 2 or 5 wk following injection. The remaining 20 mice underwent sham resection. Eight weeks following resection, necropsy and fluorescence imaging were performed to assess disease recurrence.

Results: At exploration, 39 of 40 mice had primary tumors. Eighteen of 20 mice were eligible for curative resection. Eight weeks following "curative" resection, 10 of 18 mice had recurrent disease. Of these, six developed local recurrence, two had distant metastases, and two had both.

Conclusions: Using an orthotopic animal model, we are able to reliably develop primary tumors, safely perform "curative" resection, and demonstrate a 56% recurrence rate 8 wk following resection. We confirmed disease-free resection using fluorescence imaging. This model may prove useful for preclinical adjuvant therapeutic trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Disease Progression
  • Drug Screening Assays, Antitumor
  • Mice
  • Mice, Nude
  • Neoplasm Recurrence, Local*
  • Pancreatectomy
  • Pancreatic Neoplasms / physiopathology*
  • Pancreatic Neoplasms / secondary
  • Pancreatic Neoplasms / surgery