Thioredoxin reductase activity at the surface of human primary cutaneous melanomas and their surrounding skin

Plasma membrane-associated thioredoxin reductase activities have been determined on primary melanoma tissues and their surrounding skin in 29 patients. Compared to patient's normal skin, enzyme activities in melanoma were higher in some patients (n = 24) and lower in others (n = 5). Those melanomas with high TR activities yielded low activities in the adjacent epidermis, reaching normal activity 3 to 5 cm away from each primary site (n = 4). Tumors with low activities showed higher than normal activities on the immediate surrounding skin (i.e., 1 cm away from the tumor) compared to the normal skin (n = 3). Earlier it was shown that in both keratinocytes and melanoma cells, calcium regulates thioredoxin reductase activity by an allosteric mechanism. The differences in TR activities within the high and low groups may be caused by a calcium flux between the primary tumor and the surrounding epidermis, and vice versa. A comparison of TR activities to tumor invasiveness (Breslow level) in 28 primary melanomas showed a significant correlation using regression analysis (p = 0.031). A 4-fold difference in TR activity corresponds to a one-unit change in Breslow determination. These preliminary results suggest that TR activity may be another useful and sensitive assay for melanoma spread.