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 FACS 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 35S-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.
Danen
E H
EH
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Jansen
K F
KF
Van Kraats
A A
AA
Cornelissen
I M
IM
Ruiter
D J
DJ
Van Muijen
G N
GN
D000818:Animals; D000911:Antibodies, Monoclonal; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000032:analysis*; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D011233:Precipitin Tests; D016024:Receptors, Cytoadhesin / Q000032:analysis*; D019030:Receptors, Vitronectin; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000556:secondary; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5