A Xenograft Nude Mouse Model for Perineural Invasion and Recurrence in Pancreatic Cancer

Abstract

Pancreatic cancer recurrence after initially "curative" resection is an unresolved clinical problem in the management of patients with this disease. Perineural invasion correlates with and might be partially responsible for tumor recurrence and poor survival. However, no adequate preclinical animal model is yet available to study this aspect of pancreatic cancer biology. We modified our orthotopic xenograft model of pancreatic cancer in nude mice to develop a model for pancreatic cancer perineural invasion and recurrence. After initial orthotopic transplantation, complete surgical resection of MIA PaCa-2 (undifferentiated) and Capan-2 (well-differentiated) tumors at 4, 6, and 8 weeks was attempted. All animals that had undergone tumor resection survived the operation. Animals that had the MIA PaCa-2 tumor resected after 6 weeks developed recurrent pancreatic cancer with local invasion and distant metastasis. Histological evaluation revealed extensive invasion of retroperitoneal nerves by the cancer cells. Complete resection of orthotopically transplanted pancreatic cancer in nude mice leads to local tumor recurrence. This model may eventually prove valuable for studying the mechanisms of pancreatic cancer perineural invasion and recurrence.