Search

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.

To understand the potential role of cyclooxygenase (COX) in normal and inflammatory human diseases, we characterized the expression of COX-1 and COX-2 in biopsies of osteoarthritis, atherosclerosis, and cancer. Tissues were prepared for immunohistochemistry by standard methods, and representative cases assayed via Western blot and quantitative RT-PCR. COX-2 was not detected in normal human tissues with few exceptions. Moderate to marked COX-2 was observed in the macula densa (MD) and thick ascending limb (TAL) in human fetal kidneys, but was not detected in neonatal and adult MD and TALs. Low level, constitutive COX-2 was detected in colonic epithelium, peribronchial glands, and pancreatic ductal epithelium. Low to moderate COX-2 was detected basally in the cortex, hippocampus, hypothalamus, and spinal cord, and in reproductive tissues during ovulation, implantation and labor. No COX-2 was detected in the existing vasculature in normal tissues, and was also not expressed throughout the ductus arteriosus. COX-2 was markedly induced in human tissues of osteoarthritis, atherosclerosis and cancer. COX-2 was prominently expressed in the synovium, fibrocartilage of osteophytes, and in the blood vessels in the osteoarthritic (OA) knee joint. COX-2 was also prominently detected in the macrophages/foam cells in atherosclerotic plaques, and in the endothelium overlying and immediately adjacent to the fibrofatty lesion. Moderate- to intense COX-2 expression was consistently observed in the inflammatory cells, neoplastic lesions, and blood vessels in all epithelial-derived human cancers studied. In contrast, COX-1 was relatively ubiquitously observed in both normal and pathophysiological conditions. These data collectively imply COX-2 plays an important role in mediating a variety of inflammatory diseases, and imply COX-2 inhibitors may be effective in the prevention and/or treatment of OA, heart disease, and epithelial cancers.