A Spontaneous Acinar Cell Carcinoma Model for Monitoring Progression of Pancreatic Lesions and Response to Treatment Through Noninvasive Bioluminescence Imaging

• Published in: Clinical cancer research 2009-08, Vol.15 (15), p.4915-4924
• Main Authors: NING ZHANG, LYONS, Scott, LIM, Ed, LASSOTA, Peter
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - metabolism; Antibiotics, Antineoplastic - therapeutic use; Antineoplastic agents; Biological and medical sciences; Carcinoma, Acinar Cell - drug therapy; Carcinoma, Acinar Cell - metabolism; Disease Models, Animal; Drug Monitoring; Imaging; Longitudinal Studies; Luminescent Measurements; Medical sciences; Mice; Mice, Transgenic; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pharmacology. Drug treatments; Rapamycin; Sirolimus - metabolism; Sirolimus - therapeutic use; Spontaneous acinar cell carcinoma model
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-2256

Purpose: We have generated an EL1-luc/TAg transgenic mouse model that develops spontaneous and bioluminescent acinar cell carcinomas. We applied this model to noninvasively monitor tumor development and drug response. Experimental Design: EL1-luc/TAg transgenic mice of 11 weeks of age were treated with rapamycin (5 mg/kg, i.p.) or vehicle for 6 to 12 weeks. Tumor development was monitored through bioluminescence imaging and necropsy at the study end point. Results: EL1-luc/TAg transgenic mice showed pancreas-specific bioluminescence signal before tumor progression and produced increasing light emission from the onset of the pancreatic acinar cell carcinomas. The latency of tumor development ranged from 10 to >20 weeks of age in these mice. Progression of the primary acinar cell carcinoma was accompanied by emergence of metastatic lesions in the abdominal organs, including liver and gastrointestinal fat tissues. Rapamycin treatment suppressed tumor development. Conclusions: The EL1-luc/TAg mouse provides a noninvasive approach for monitoring spontaneous acinar cell carcinoma development and comprises a convenient tool for the evaluation of novel therapeutics against pancreatic cancers. Tumor growth suppression through inhibition of the mammalian target of rapamycin pathway further validates this model as clinically relevant.