Melanoma cell-cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion.
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.
Shih
I M
IM
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Speicher
D
D
Hsu
M Y
MY
Levine
E
E
Herlyn
M
M
D015703:Antigens, CD; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects; D002450:Cell Communication / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019006:Neural Cell Adhesion Molecules; D011509:Proteoglycans; D011994:Recombinant Proteins; C497902:MCAM protein, human