MEMD, A NEW CELL-ADHESION MOLECULE IN METASTASIZING HUMAN-MELANOMA CELL-LINES, IS IDENTICAL TO ALCAM (ACTIVATED LEUKOCYTE CELL-ADHESION MOLECULE)

From a differential mRNA display comparing a non- and a highly metasta sizing human melanoma cell line, we isolated and characterized memD. m emD is preferentially expressed in the highly metastasizing melanoma c ell lines of a larger panel. The encoded protein, MEMD, is identical t o activated leukocyte cell adhesion molecule (ALCAM), a recently ident ified Ligand of CD6. ALCAM is involved in homophylic (ALCAM-ALCAM) and heterophylic (ALCAM-CD6) cell adhesion interactions. We have studied MEMD/ALCAM cell-cell interactions between human melanoma cells. The ex pression of this cell adhesion molecule not only correlates with enhan ced metastatic properties and with aggregational behavior of human mel anoma cells as tested by FACS analysis, but transfection experiments a lso make clear that MEMD/ALCAM expression is essential for cell-cell i nteraction of the investigated human melanoma cells. As the melanoma c ell lines analyzed are all CD6 negative, these results strongly sugges t that MEMD/ALCAM is an adhesion molecule mediating homophylic cluster ing of melanoma cells. MEMD/ALCAM expression is not restricted to subs ets of leukocytes and melanoma cells, it can also be found in healthy organs and in several other malignant tumor cell Lines. Besides, MEMD/ ALCAM is also expressed in cultured endothelial cells, pericytes and m elanocytes, in xenografts derived from the radial and vertical growth phase and in 4 of 13 melanoma metastasis lesions. The potential role i s discussed of MEMD/ALCAM mediated cell-cell interactions in migration of mobile cells (ie, activated leukocytes, metastasizing tumor cells) through tissues.