Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression.
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.
Goulet
A-C
AC
Department of Pathology, University of Arizona, Tucson, Arizona 85724, USA.
Einsphar
Janine G
JG
Alberts
David S
DS
Beas
Anthony
A
Burk
Cynthia
C
Bhattacharyya
Achyut
A
Bangert
Jerry
J
Harmon
Janet M
JM
Fujiwara
Hideji
H
Koki
Alane
A
Nelson
Mark A
MA
D000328:Adult; D000368:Aged; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D016895:Culture Media, Serum-Free; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology*; D008565:Membrane Proteins; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D006893:Hydroxyeicosatetraenoic Acids; D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D008084:Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases