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 NOT TO METASTATIC CAPACITY OF CELL-LINES IN NUDE-MICE

We investigated the expression of alpha(v)-integrins in different stages of human cutaneous melanocytic tumor progression. We observed that alpha(v) beta(5) was the alpha(v)-integrin expressed in all common nevocellular nevi, in 78% of dysplastic nevi, in 63% of early primary melanomas, in 43% of advanced primary melanomas, and in 33% of melanoma metastases. Hence, loss of alpha(v) beta(5) expression was related to melanocytic tumor progression. In line with earlier reports, alpha(v) beta(3) was exclusively detected in advanced primary melanomas and metastases (24% and 50% respectively). Staining with anti-alpha(v) monoclonal antibodies (MAbs) in lesions where both alpha(v) beta(3) and alpha(v) beta(5) were absent showed that alternative alpha(v)-integrins were expressed in advanced primary melanomas and metastases. By FAGS analysis, 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 both highly metastatic cell lines expressed alpha(v) beta(5) at their surface. 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 from S-35-methionine-labeled cells and by absence of immunohistochemical staining on primary and metastatic xenograft lesions. Our findings indicate that alpha(v) beta(5) expression is often lost in advanced stages 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 alpha(v) beta(3) expression are not necessarily related to the metastatic behavior of human melanoma cells in nude mice. (C) 1995 Wiley-Liss, Inc.