Many steps in
melanoma metastasis involve cell-cell or cell-matrix adhesive interactions. The surface molecules which mediate these processes therefore play an important role in regulating
melanoma dissemination and their level of expression may alter during the course of
tumor progression. Human melanocyte strains and
melanoma cell lines have been characterised with regard to levels of
cell surface receptors of the
integrin family. Increased amounts of at least two
integrins,
VLA-4 (alpha 4 beta 1) and VnR (alpha v beta 3), appeared to correlate with progression in this
tumor, type. A novel VnR composed of an alpha v beta 1 association has been observed in one
melanoma cell line and there is the possibility that heterogeneity of
integrin composition could affect
biological behavior of these
tumors. CD44, a
cell surface glycoprotein which functions as the major receptor for hyaluronate, is another molecule whose expression increases in transformed cells of the melanocytic lineage. Iterative sorting on the FACS for stable variants, of both human and murine
melanomas, expressing low and high levels of CD44 established that lack of expression of this molecule correlated with impaired ability to form pulmonary
tumor nodules subsequent to i.v. injection into appropriate recipient mice. These findings illustrate that an understanding of the regulation of
melanoma adhesion receptors could provide insights into the process of
tumor spread.