IN-SITU DISTRIBUTION OF INTEGRIN ALPHA(2)BETA(1) AND ALPHA-ACTININ INMELANOCYTIC PROLIFERATIONS

Integrin alpha(2) beta(1) is a transmembrane protein receptor for coll agen and laminin previously reported as a melanoma tumor progression a ntigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta(1)-integrin chain of alpha(2) beta(1). In vitro both alpha(2) beta(1) and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line moti lity (measured as mean migration rates), correlates with metastasis. T o determine the in situ distribution of these proteins, we used monocl onal antibodies directed against the alpha(2)-integrin subunit of alph a(2) beta(1) and alpha-actinin on frozen sections of 33 melanocytic pr oliferations, which included dermal nevi, primary melanomas, and metas tatic melanomas. We found that the superficial portion of all of the m elanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of s taining for alpha-actinin in the cells in the deep reticular dermis. I n contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha(2) beta(1); the expression of this protein correlated with the later stages of mel anoma progression. Our findings suggest that alpha-actinin protein lev els initially decrease and then increase during melanocytic tumor prog ression, whereas the alpha(2) subunit protein appears in the later sta ges of melanoma progression. The variable distribution of these protei ns is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations.