Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line.

CD63 belongs to the transmembrane 4 superfamily of membrane proteins and is expressed in several normal tissues as well as in melanoma cells. Previous reports have suggested that CD63 may play an important role in inhibiting melanoma progression, and this was supported by our studies showing that CD63 was associated with suppression of the growth of melanoma in nude mice. Recently, we and others have shown that CD63 may form noncovalent associations with beta1 integrins, which suggests that the function of CD63 may be related to that of integrins. To further explore the role of CD63 in melanoma, we transfected CD63 into a highly motile, CD63-negative melanoma cell line, KM3, which was shown to express alpha(v)beta5 as the predominant integrin with only trace amounts of beta1 integrins. Following transfection, CD63 was shown to associate with beta1 integrins, and beta1 expression appeared to be up-regulated. Cell motility in serum-containing media was markedly suppressed following transfection of CD63. This inhibition was potentiated by mAbs to CD63, and correlated with the level of CD63 expression. The CD63-transfected, but not the untransfected, melanoma cells showed increased adhesion and migration on the beta1 substrates, fibronectin, laminin, and collagen, whereas rates of migration were similar on the beta5 substrate, vitronectin. These results show that CD63 is involved in regulation of the motility of melanoma cells and their adhesion and migration on substrates associated with beta1 integrins. We suggest they provide further insights into the role of CD63 in tumor progression.