Expression of cyclooxygenase 2 in human malignant melanoma

Cyclooxygenase (COX)-2 is an inducible enzyme involved in production of prostaglandins in inflammatory processes. There is now increasing evidence that a constitutive expression of COX-2 plays a role in development and progression of malignant epithelial tumors. In the present study we investigated expression and function of COX-2 in malignant melanoma. Expression of COX-2 was determined by immunohistochemistry in 28 cases of primary skin melanoma and 4 benign nevi. We show that COX-2 was expressed in 26 cases (93%) of melanomas, with a moderate to strong expression in 19 cases (68%). Benign nevi as well as normal epithelium sere negative in all cases. A constitutive expression of COX-2 mRNA and protein was found in five melanoma cell lines (A375, MeWo, SK-MeL-13, SK-Mel-28, and IGR-37) by using Northern blot as well as immunoblotting. All melanoma cell, lines produced prostaglandin (PG) E-2 between 468 and 3500 pg/ml as determined by ELISA. Treatment with NS-398 (50 muM), a specific inhibitor of COX-2, suppressed PGE(2) production of all melanoma cell lines by 50-96 %. The IC50 for inhibition of PGE(2) production by NS-398 was determined as 4 muM, indicating that NS-398 acts via inhibition of the COX-2 isoenzyme. We could show that proliferation of melanoma cell lines was not influenced by treatment with NS-398 in concentrations up to 100 muM. However, NS-398 reduced Matrigel invasion of all five malignant melanoma cell lines by 50-68%. Our results indicate that COX-2 is expressed in malignant melanomas and may be involved in regulation of melanoma invasion. It remains to be investigated whether selective inhibitors of COX-2 might be useful for prevention or treatment of malignant melanoma.