Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression

Cancer Biol Ther. Nov-Dec 2003;2(6):713-8.

Abstract

Cyclooxygenase 2 (COX-2) is an inducible enzyme involved in the production of prostaglandins and thromboxanes during inflammation. There are now several lines of evidence indicating that increased expression of COX-2 plays a functional role in the development and progression of malignant epithelial cancers. However, there is only limited data regarding the role of COX-2 in melanoma pathogenesis. In the present work, we retrospectively examined lesions through out the development of melanoma and metastatic disease (dysplastic nevi n = 10, melanoma in situ n = 4, stage II melanoma n = 10, stage III n = 4, stage IV n = 3, stage V n = 2, melanoma metastasis lymph nodes n = 13 metastasis to other sites n = 3). COX-2 was consistently observed in keratinocytes, dermal fibroblasts, and inflammatory cells in regions adjacent to benign evi and primary cutaneous melanomas. However, no COX-2 staining was detected in the nevi nor in the primary skin melanoma cells. In addition, COX-2 was undetected in all vertical and radial growth phase cases Interestingly, 13 out of 13 of the lymph node metastasis expressed extremely high levels of COX-2 in overlying epithelium and inflammatory cells, and COX-2 was strongly detected in the metastatic cancer cells per se. For additional information on the expression of COX-2 in malignant melanoma, we determined the expression of COX-2 protein in several different melanoma cell lines. We found that 3We found that 5 out of 7 of the melanoma cells over expressed COX-2 compared to normal melanocytes. Collectively, these data suggest that COX-2 may play a functional role in metastases of melanoma, and treatment with COX-2 inhibitors may be efficacious for malignant melanoma.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Arachidonic Acid / pharmacology
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Culture Media, Serum-Free
  • Cyclooxygenase 2
  • Disease Progression
  • Female
  • Fibroblasts / enzymology
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Immunohistochemistry
  • Isoenzymes / analysis
  • Isoenzymes / metabolism*
  • Lipoxygenase / metabolism
  • Lymph Nodes / pathology
  • Male
  • Mass Spectrometry
  • Melanocytes / enzymology
  • Melanoma / enzymology*
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / metabolism*

Substances

  • Culture Media, Serum-Free
  • Hydroxyeicosatetraenoic Acids
  • Isoenzymes
  • Membrane Proteins
  • Arachidonic Acid
  • Lipoxygenase
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases