An Immunocompetent Mouse Model of Surgical Resection and Recurrence in Pancreatic Cancer
Abstract
ObjectiveSurgical resection is the only curative treatment for pancreatic cancer but almost all patients who undergo resection will eventually develop local and/or distant recurrence. We aim to develop a reliable... [ view full abstract ]
Objective
Surgical resection is the only curative treatment for pancreatic cancer but almost all patients who undergo resection will eventually develop local and/or distant recurrence. We aim to develop a reliable immuno-competent model for resection and recurrence with a micro-environment that closely recapitulates human disease.
Methods
Cancer cells from a genetic model of pancreatic cancer, KrasLSLG12D/+;p53R172H/+; PdxCre-/+ (KPC), were harvested and co-injected with wild type stellate cells(PSC) into the pancreas of immunocompetent C57B6(WT) mice to re-capitulate a desmoplastic tumor. Mice bearing tumors were then serially resected at 4, 10 and 20 days post-tumor implantation. This model was then used to characterize recurrence patterns and evaluate chemotherapy.
Results
Co-injection of KPC cells and WT PSCs formed tumors that closely recapitulated the dense desmoplastic stroma of human disease. Resection at 20 days post tumor implantation revealed tumors that were of uniform size (about 450 mm3) and were mostly localized to the pancreas. Resection margins were also free of tumors on histologic assessment thus allowing R0 resection. Recurrence of local and distant disease was almost universal strongly mimicking human disease. Adjuvant chemotherapy using paclitaxel and gemcitabine was able to prolong survival in these mice compared to mice no treatment or only resection.
Conclusion
Our study describes a reliable model of pancreatic tumor resection and recurrence that is modeled in an immuno-competent setting and closely resembles the dense desmoplasia of human PDAC. Further characterization will provide a valuable tool to study patterns of recurrence and design novel strategies to treat recurrence in pancreatic cancer.
Authors
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Bhuwan Giri
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Shrey Modi
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Vrishketan Sethi
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Bharti Garg
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Sulagna Banerjee
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Ashok Saluja
(University of Miami – Miller School of Medicine, Miami, Florida, USA)
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Vikas Dudeja
(University of Miami Leonard M. Miller School of Medicine, Miami, Florida, U.S.A.)
Topic Area
Surgical Oncology
Session
QS-SurgOnc » Quick-Shot Presentations: Surgical Oncology (15:00 - Thursday, 21st September, Lee 404)