Document Type
Article
Publication Date
2006
Publication Title
Neoplasia
First Page
437
Last Page
445
DOI
http://dx.doi.org/10.1593/neo.04700
Abstract
Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.
Rights
Originally published by Elsevier under a Creative Commons License in Neoplasia, 2006, Volume 8, Issue 6. DOI: 10.1593/neo.04700.
Recommended Citation
Crowell, Pamela L.; Schmidt, C. Max; Yip-Schneider, Michele T.; Savage, Jesse J.; Hertzler, Dean A. II; and Cummings, William O., "Cyclooxygenase-2 Expression in Hamster and Human Pancreatic Neoplasia" (2006). Scholarship and Professional Work – COPHS. 136.
https://digitalcommons.butler.edu/cophs_papers/136
