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 metastasizing human melanoma cell line, we isolated and characterized memD. memD is preferentially expressed in the highly metastasizing melanoma cell lines of a larger panel. The encoded protein, MEMD, is identical to activated leukocyte cell adhesion molecule (ALCAM), a recently identified 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 expression of this cell adhesion molecule not only correlates with enhanced metastatic properties and with aggregational behavior of human melanoma cells as tested by FACS analysis, but transfection experiments also make clear that MEMD/ALCAM expression is essential for cell-cell interaction of the investigated human melanoma cells. As the melanoma cell lines analyzed are all CD6 negative, these results strongly suggest that MEMD/ALCAM is an adhesion molecule mediating homophylic clustering of melanoma cells. MEMD/ALCAM expression is not restricted to subsets 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 melanocytes, in xenografts derived from the radial and vertical growth phase and in 4 of 13 melanoma metastasis lesions. The potential role is discussed of MEMD/ALCAM mediated cell-cell interactions in migration of mobile cells (ie, activated leukocytes, metastasizing tumor cells) through tissues.

[1]  D. Ruiter,et al.  Establishment and characterization of a human melanoma cell line (MV3) which is highly metastatic in nude mice , 2007, International journal of cancer.

[2]  J. Johnson,et al.  Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. , 1997, Cancer research.

[3]  M. Egmond,et al.  nmd, a novel gene differentially expressed in human melanoma cell lines, encodes a new atypical member of the enzyme family of lipases , 1997, FEBS letters.

[4]  R. Maini,et al.  Manual of Biological Markers of Disease , 1996, Springer Netherlands.

[5]  J. Bajorath,et al.  Mutational analysis of the CD6 binding site in activated leukocyte cell adhesion molecule. , 1996, Biochemistry.

[6]  J. Bajorath,et al.  The Amino-terminal Immunoglobulin-like Domain of Activated Leukocyte Cell Adhesion Molecule Binds Specifically to the Membrane-proximal Scavenger Receptor Cysteine-rich Domain of CD6 with a 1:1 Stoichiometry* , 1996, The Journal of Biological Chemistry.

[7]  O. Pourquié,et al.  BEN/SC1/DM-GRASP, a homophilic adhesion molecule, is required for in vitro myeloid colony formation by avian hemopoietic progenitors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. V. van Kessel,et al.  Expression of nma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts , 1996, International journal of cancer.

[9]  H. Bloemers,et al.  Identification of melanoma inhibitory activity and other differentially expressed messenger RNAs in human melanoma cell lines with different metastatic capacity by messenger RNA differential display. , 1995, Cancer Research.

[10]  B. Haynes,et al.  Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand , 1995, The Journal of experimental medicine.

[11]  B. Haynes,et al.  Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells , 1995, The Journal of experimental medicine.

[12]  N. Ajubi,et al.  nmb, a novel gene, is expressed in low‐metastatic human melanoma cell lines and xenografts , 1995, International journal of cancer.

[13]  D. Elder,et al.  Isolation and functional characterization of the A32 melanoma-associated antigen. , 1994, Cancer research.

[14]  A. Bartolazzi,et al.  Integrin expression in cutaneous malignant melanoma: Association of the α3/β1 heterodimer with tumor progression , 1993 .

[15]  J. Rossier,et al.  BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[16]  O. Pourquié,et al.  An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes. , 1992, Cellular immunology.

[17]  J. Kuźnicki,et al.  Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice. , 1992, Cancer research.

[18]  T. Krieg,et al.  Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils , 1991, The Journal of cell biology.

[19]  H. Phillips,et al.  Molecular cloning and expression of a novel adhesion molecule, SC1 , 1991, Neuron.

[20]  J. Kamholz,et al.  DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension , 1991, Neuron.

[21]  J. Lehmann,et al.  MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[22]  W. Birchmeier,et al.  Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion , 1989, The Journal of cell biology.

[23]  P. Hoffman,et al.  Antibody-induced antigenic modulation is antigen dependent: characterization of 22 proteins on a malignant human B cell line. , 1986, Journal of immunology.

[24]  C. Cepko,et al.  Construction and applications of a highly transmissible murine retrovirus shuttle vector , 1984, Cell.

[25]  M. Herlyn,et al.  Adhesion receptors in human melanoma progression. , 1994, Invasion & metastasis.

[26]  C. Bucana,et al.  Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. , 1993, Melanoma research.

[27]  J. Covault,et al.  Characterization of a cell surface adhesion molecule expressed by a subset of developing chick neurons. , 1992, Developmental biology.

[28]  G. Riethmüller,et al.  De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  P. Devilee,et al.  Two subsets of human alphoid repetitive DNA show distinct preferential localization in the pericentric regions of chromosomes 13, 18, and 21. , 1986, Cytogenetics and cell genetics.