Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia

Pamela L. Crowell, C. Max Schmidt, Michele T. Yip-Schneider, Jesse J. Savage, Dean A. Hertzler, William O. Cummings

Research output: Contribution to journalArticle

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalNeoplasia
Volume8
Issue number6
DOIs
StatePublished - Jan 1 2006

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Keywords

  • Chemical carcinogenesis
  • COX-2
  • Pancreatic neoplasms
  • PanIN
  • Sulindac

ASJC Scopus subject areas

  • Cancer Research

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