Expression of cyclooxygenase 2 in human malignant melanoma

Cyclooxygenase (COX)-2 is an inducible enzyme involved in production of pro staglandins in inflammatory processes. There is now increasing evidence tha t a constitutive expression of COX-2 plays a role in development and progre ssion 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 melanom a 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 n evi 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 w ell as immunoblotting. All melanoma cell, lines produced prostaglandin (PG) E-2 between 468 and 3500 pg/ml as determined by ELISA. Treatment with NS-3 98 (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) prod uction by NS-398 was determined as 4 muM, indicating that NS-398 acts via i nhibition of the COX-2 isoenzyme. We could show that proliferation of melan oma cell lines was not influenced by treatment with NS-398 in concentration s up to 100 muM. However, NS-398 reduced Matrigel invasion of all five mali gnant melanoma cell lines by 50-68%. Our results indicate that COX-2 is exp ressed in malignant melanomas and may be involved in regulation of melanoma invasion. It remains to be investigated whether selective inhibitors of CO X-2 might be useful for prevention or treatment of malignant melanoma.