1887
Volume 2013, Issue 1
  • ISSN: 2220-2749
  • E-ISSN:

Abstract

Prostaglandins, in particular prostaglandin E (PGE), are elevated in adenomas and colorectal cancers (CRC). Experimental and epidemiological studies have demonstrated reduced incidence of adenomas and CRC by inhibitors of prostanoid synthesis (NSAIDs). This study aimed to characterize the expression and localization of key enzymes/receptors for PGE synthesis in adenomas and CRC in comparison to normal colon. Immunoblotting and immunohistochemistry were used for semi-quantitative and qualitative analysis of COX-1, COX-2, mPGES-1 and the EP receptor in biopsies from patients undergoing resection of adenomas or surgery for CRC (Dukes' A-C). Normal colon served as control for the corresponding tumor in each of the CRC patients. COX-1 was decreased significantly in all groups of CRC (Dukes' A-C) compared to normal colon. In contrast, COX-2 was increased, but only in the combined group of CRC. Microsomal PGES-1 was increased in CRC (Duke's B), and EP was augmented in adenomas and CRC. The localization was predominantly epithelial in normal colon and in adenomas, while in CRC both epithelial- and stromal expression was demonstrated. The results support the PGE- pathway, with epithelial- stromal interactions, in the evolvement of adenomas and in the progression of CRC. Co-expression of COX-1 and COX-2 is in line with the preventive effects of non-specific NSAIDs on adenoma formation. The decrease of COX-1, in combination with an increase of COX-2, favors the potential use of selective COX-2 inhibitors as an adjunct therapy in CRC.

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2013-09-01
2019-10-17
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