αvβ3 expression on blood vessels and melanoma cells in primary lesions; differential association with tumor progression and clinical prognosis

The α v β 3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of α v β 3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information is available about the clinical significance of α v β 3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that α v β 3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared α v β 3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we have examined the lesions for expression of the α v subunit to gain information on the regulation of α v β 3 expression on endothelial cells and on cells of the melanocyte lineage. α v β 3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions. However, α v β 3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The α v subunit and the α v β 3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways control their expression. This finding may account for the differential clinical significance of α v β 3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, α v β 3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of all metastatic lesions tested and its restricted distribution in normal tissues.