Melanoma cell-cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion.

Abstract

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.

• Authors: I M Shih, D Speicher, M Y Hsu, E Levine, M Herlyn
• Journal: Cancer research (Cancer Res) Vol. 57 Issue 17 Pg. 3835-40 (Sep 01 1997) ISSN: 0008-5472 [Print] United States
• PMID: 9288796 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• CD146 Antigen
• Cell Adhesion Molecules
• Heparan Sulfate Proteoglycans
• MCAM protein, human
• Membrane Glycoproteins
• Neoplasm Proteins
• Neural Cell Adhesion Molecules
• Proteoglycans
• Recombinant Proteins
• Heparitin Sulfate

Topics

• Antigens, CD
• CD146 Antigen
• Cell Adhesion Molecules (metabolism, physiology)
• Cell Aggregation (drug effects)
• Cell Communication (physiology)
• Heparan Sulfate Proteoglycans
• Heparitin Sulfate (metabolism)
• Humans
• Melanoma (metabolism, pathology, physiopathology)
• Membrane Glycoproteins (metabolism, physiology)
• Neoplasm Proteins (metabolism, physiology)
• Neural Cell Adhesion Molecules
• Proteoglycans (metabolism)
• Recombinant Proteins
• Tumor Cells, Cultured