Prostaglandin E(2) pathway in head and neck squamous cell carcinoma

Head Neck. 2008 Sep;30(9):1175-81. doi: 10.1002/hed.20850.

Abstract

Background: Prostaglandin E(2) (PGE(2)) is involved in malignant growth. The objective was to study the PGE(2) pathway in head and neck squamous cell carcinoma (HNSCC) patients.

Methods: Expression of cyclooxygenase (COX) and PGE-synthase isoenzymes, and PGE-receptors was determined in biopsies from 83 patients with HNSCC by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Expression of COX-2 and cytosolic-PGE-synthase was significantly increased, about 4-fold and 2.5-fold, respectively, in tumors versus paired nontumoral mucosa (n = 34). EP-1 was the only PGE-receptor significantly overexpressed in tumor samples. Expression of COX-1 correlated with mPGES-2 and COX-2 correlated with mPGES-1 (n = 83).

Conclusions: COX-2, functionally coordinated with mPGES-1, is likely to be the limiting enzyme in PGE(2) biosynthesis in HNSCC. The biological meaning of cPGES/p23 overexpression in HNSCC is not yet clear. Our results support the notion that mPGES-1, cPGES, and EP-1 could be the targets for the development of specific PGE(2)-modifier drugs for HNSCC treatment that could avoid negative side effects of COX-2 selective inhibitors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Biopsy, Needle
  • Biosynthetic Pathways
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology
  • Cyclooxygenase 1 / metabolism*
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase Inhibitors / therapeutic use
  • Dinoprostone / metabolism*
  • Female
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / metabolism*
  • Isoenzymes / biosynthesis
  • Male
  • Microsomes / metabolism
  • Prostaglandin-E Synthases
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • RNA, Messenger
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • PTGES2 protein, human
  • Prostaglandin-E Synthases
  • Dinoprostone