αv‐Integrins in human melanoma: Gain of αvβ3 and loss OF αvβ5 are related to tumor progression in situ but not to metastatic capacity of cell lines in nude mice

We investigated the expression of αv‐integrins in different stages of human cutaneous melanocytic tumor progression. We observed that αvβ5 was the αv‐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 αvβ5 expression was related to melanocytic tumor progression. In line with earlier reports, αvβ3 was exclusively detected in advanced primary melanomas and metastases (24% and 50% respectively). Staining with anti‐αv monoclonal antibodies (MAbs) in lesions where both αvβ3 and αvβ5 were absent showed that alternative αv‐integrins were expressed in advanced primary melanomas and metastases. By FACS analysis, we determined expression of αvβ5 and αvβ3 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 αvβ5 at their surface. Surprisingly, αvβ3 was detected exclusively in the non‐metastatic cell lines. Absence of αvβ3 in the highly metastatic cell lines was confirmed by lack of immunoprecipitation from 35S‐methionine‐labeled cells and by absence of immunohistochemical staining on primary and metastatic xenograft lesions. Our findings indicate that αvβ5 expression is often lost in advanced stages of melanocytic tumor progression in situ, while αvβ3 is acquired, but that a decrease in αvβ5 and an increase in αvβ3 expression are not necessarily related to the metastatic behavior of human melanoma cells in nude mice. © 1995 Wiley‐Liss, Inc.