ALPHA(V)-INTEGRINS IN HUMAN-MELANOMA - GAIN OF ALPHA(V)BETA(3) AND LOSS OF ALPHA(V)BETA(5) ARE RELATED TO TUMOR PROGRESSION IN-SITU BUT NOTTO METASTATIC CAPACITY OF CELL-LINES IN NUDE-MICE

We investigated the expression of alpha(v)-integrins in different stag es of human cutaneous melanocytic tumor progression. We observed that alpha(v) beta(5) was the alpha(v)-integrin expressed in all common nev ocellular nevi, in 78% of dysplastic nevi, in 63% of early primary mel anomas, in 43% of advanced primary melanomas, and in 33% of melanoma m etastases. Hence, loss of alpha(v) beta(5) expression was related to m elanocytic tumor progression. In line with earlier reports, alpha(v) b eta(3) was exclusively detected in advanced primary melanomas and meta stases (24% and 50% respectively). Staining with anti-alpha(v) monoclo nal antibodies (MAbs) in lesions where both alpha(v) beta(3) and alpha (v) beta(5) were absent showed that alternative alpha(v)-integrins wer e expressed in advanced primary melanomas and metastases. By FAGS anal ysis, we determined expression of alpha(v) beta(5) and alpha(v) beta(3 ) in 4 human melanoma cell lines with different metastatic capacities after s.c. inoculation into nude mice. One of the non-metastatic and b oth highly metastatic cell lines expressed alpha(v) beta(5) at their s urface. Surprisingly, alpha(v) beta(3) was detected exclusively in the non-metastatic cell lines. Absence of alpha(v) beta(3) in the highly metastatic cell lines was confirmed by lack of immunoprecipitation fro m S-35-methionine-labeled cells and by absence of immunohistochemical staining on primary and metastatic xenograft lesions. Our findings ind icate that alpha(v) beta(5) expression is often lost in advanced stage s of melanocytic tumor progression in situ, while alpha(v) beta(3) is acquired, but that a decrease in alpha(v) beta(5) and an increase in a lpha(v) beta(3) expression are not necessarily related to the metastat ic behavior of human melanoma cells in nude mice. (C) 1995 Wiley-Liss, Inc.