Mel-
cell adhesion molecule (CAM), also known as MUC18 and CD146, is a novel member of the
immunoglobulin supergene family. Mel-CAM was first identified as an integral
membrane glycoprotein in human
melanoma and is also abundantly expressed by endothelial cells of various origins. In a previous study (I. M. Shih et al.,
Cancer Res., 54: 2514-2520, 1994), we showed that Mel-CAM is a cell-
cell adhesion molecule with a possible role in
melanoma invasion and
metastasis. Here, we define the molecular mechanism responsible for cell-cell adhesion of Mel-CAM and demonstrate its role in
melanoma-endothelial cell interactions. Most of human
melanoma cells, including Mel-CAM-negative SBcl-2 cells, adhered to
nitrocellulose-immobilized Mel-CAM produced by baculovirus recombinants. This adhesion can be blocked by full-length Mel-CAM or polyclonal antiserum against Mel-CAM. Adhesion is not affected by the presence of
EDTA, truncated Mel-CAM extracellular domain, or
heparan sulfate proteoglycan. In cell aggregation assays, Mel-CAM-negative SBcl-2 cells cluster with U937TM cells (U937 transfected with Mel-CAM
cDNA) but not with control nontransfectants, suggesting that SBcl-2 cells express the
ligand for Mel-CAM. SBcl-2 cells also form heterotypic aggregates with Mel-CAM-positive human endothelial cells but not with Mel-CAM-negative but
ligand-positive smooth muscle cells. Taken together, our results show that Mel-CAM mediates cell-cell adhesion through heterophilic adhesion to an as yet unidentified
ligand present on
melanoma but not on endothelial cells. Thus,
melanoma-endothelial interactions during
metastasis may occur through this novel mechanism.