Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1998 Mar;152(3):805–813.

MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule).

W G Degen 1, L C van Kempen 1, E G Gijzen 1, J J van Groningen 1, Y van Kooyk 1, H P Bloemers 1, G W Swart 1
PMCID: PMC1858405  PMID: 9502422

Abstract

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.

Full text

PDF
805

Images in this article

807Figure 1
on p.807
808Figure 2
on p.808
808Figure 3
on p.808
809Figure 5
on p.809
810Figure 7
on p.810
810Figure 8
on p.810
811Figure 9
on p.811

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993 Jan;68(1):4–17. [PubMed] [Google Scholar]
  2. Behrens J., Mareel M. M., Van Roy F. M., Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. doi: 10.1083/jcb.108.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowen M. A., Bajorath J., Siadak A. W., Modrell B., Malacko A. R., Marquardt H., Nadler S. G., Aruffo A. 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. J Biol Chem. 1996 Jul 19;271(29):17390–17396. doi: 10.1074/jbc.271.29.17390. [DOI] [PubMed] [Google Scholar]
  4. Bowen M. A., Patel D. D., Li X., Modrell B., Malacko A. R., Wang W. C., Marquardt H., Neubauer M., Pesando J. M., Francke U. Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand. J Exp Med. 1995 Jun 1;181(6):2213–2220. doi: 10.1084/jem.181.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burns F. R., von Kannen S., Guy L., Raper J. A., Kamholz J., Chang S. DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. Neuron. 1991 Aug;7(2):209–220. doi: 10.1016/0896-6273(91)90259-3. [DOI] [PubMed] [Google Scholar]
  6. Cepko C. L., Roberts B. E., Mulligan R. C. Construction and applications of a highly transmissible murine retrovirus shuttle vector. Cell. 1984 Jul;37(3):1053–1062. doi: 10.1016/0092-8674(84)90440-9. [DOI] [PubMed] [Google Scholar]
  7. Corbel C., Bluestein H. G., Pourquie O., Vaigot P., Le Douarin N. M. An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes. Cell Immunol. 1992 Apr 15;141(1):99–110. doi: 10.1016/0008-8749(92)90130-h. [DOI] [PubMed] [Google Scholar]
  8. Corbel C., Pourquié O., Cormier F., Vaigot P., Le Douarin N. M. BEN/SC1/DM-GRASP, a homophilic adhesion molecule, is required for in vitro myeloid colony formation by avian hemopoietic progenitors. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2844–2849. doi: 10.1073/pnas.93.7.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Degen W. G., Weterman M. A., van Groningen J. J., Cornelissen I. M., Lemmers J. P., Agterbos M. A., Geurts van Kessel A., Swart G. W., Bloemers H. P. Expression of nma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts. Int J Cancer. 1996 Feb 8;65(4):460–465. doi: 10.1002/(SICI)1097-0215(19960208)65:4<460::AID-IJC12>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  10. Devilee P., Cremer T., Slagboom P., Bakker E., Scholl H. P., Hager H. D., Stevenson A. F., Cornelisse C. J., Pearson P. L. Two subsets of human alphoid repetitive DNA show distinct preferential localization in the pericentric regions of chromosomes 13, 18, and 21. Cytogenet Cell Genet. 1986;41(4):193–201. doi: 10.1159/000132229. [DOI] [PubMed] [Google Scholar]
  11. Gehlsen K. R., Davis G. E., Sriramarao P. Integrin expression in human melanoma cells with differing invasive and metastatic properties. Clin Exp Metastasis. 1992 Mar;10(2):111–120. doi: 10.1007/BF00114587. [DOI] [PubMed] [Google Scholar]
  12. Johnson J. P., Stade B. G., Holzmann B., Schwäble W., Riethmüller G. De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci U S A. 1989 Jan;86(2):641–644. doi: 10.1073/pnas.86.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klein C. E., Dressel D., Steinmayer T., Mauch C., Eckes B., Krieg T., Bankert R. B., Weber L. 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. J Cell Biol. 1991 Dec;115(5):1427–1436. doi: 10.1083/jcb.115.5.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lehmann J. M., Riethmüller G., Johnson J. P. MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9891–9895. doi: 10.1073/pnas.86.24.9891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Luca M., Hunt B., Bucana C. D., Johnson J. P., Fidler I. J., Bar-Eli M. Direct correlation between MUC18 expression and metastatic potential of human melanoma cells. Melanoma Res. 1993 Feb;3(1):35–41. doi: 10.1097/00008390-199304000-00006. [DOI] [PubMed] [Google Scholar]
  16. Natali P. G., Nicotra M. R., Bartolazzi A., Cavaliere R., Bigotti A. Integrin expression in cutaneous malignant melanoma: association of the alpha 3/beta 1 heterodimer with tumor progression. Int J Cancer. 1993 Apr 22;54(1):68–72. doi: 10.1002/ijc.2910540112. [DOI] [PubMed] [Google Scholar]
  17. Nesbit M., Herlyn M. Adhesion receptors in human melanoma progression. Invasion Metastasis. 1994;14(1-6):131–146. [PubMed] [Google Scholar]
  18. Patel D. D., Wee S. F., Whichard L. P., Bowen M. A., Pesando J. M., Aruffo A., Haynes B. F. Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells. J Exp Med. 1995 Apr 1;181(4):1563–1568. doi: 10.1084/jem.181.4.1563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pesando J. M., Hoffman P., Abed M. Antibody-induced antigenic modulation is antigen dependent: characterization of 22 proteins on a malignant human B cell line. J Immunol. 1986 Dec 1;137(11):3689–3695. [PubMed] [Google Scholar]
  20. Pourquié O., Corbel C., Le Caer J. P., Rossier J., Le Douarin N. M. BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5261–5265. doi: 10.1073/pnas.89.12.5261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shih I. M., Elder D. E., Speicher D., Johnson J. P., Herlyn M. Isolation and functional characterization of the A32 melanoma-associated antigen. Cancer Res. 1994 May 1;54(9):2514–2520. [PubMed] [Google Scholar]
  22. Skonier J. E., Bowen M. A., Emswiler J., Aruffo A., Bajorath J. Mutational analysis of the CD6 binding site in activated leukocyte cell adhesion molecule. Biochemistry. 1996 Nov 26;35(47):14743–14748. doi: 10.1021/bi961905l. [DOI] [PubMed] [Google Scholar]
  23. Tanaka H., Matsui T., Agata A., Tomura M., Kubota I., McFarland K. C., Kohr B., Lee A., Phillips H. S., Shelton D. L. Molecular cloning and expression of a novel adhesion molecule, SC1. Neuron. 1991 Oct;7(4):535–545. doi: 10.1016/0896-6273(91)90366-8. [DOI] [PubMed] [Google Scholar]
  24. Van Muijen G. N., Cornelissen L. M., Jansen C. F., Figdor C. G., Johnson J. P., Bröcker E. B., Ruiter D. J. Antigen expression of metastasizing and non-metastasizing human melanoma cells xenografted into nude mice. Clin Exp Metastasis. 1991 May-Jun;9(3):259–272. doi: 10.1007/BF01753729. [DOI] [PubMed] [Google Scholar]
  25. Weterman M. A., Ajubi N., van Dinter I. M., Degen W. G., van Muijen G. N., Ruitter D. J., Bloemers H. P. nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. Int J Cancer. 1995 Jan 3;60(1):73–81. doi: 10.1002/ijc.2910600111. [DOI] [PubMed] [Google Scholar]
  26. Weterman M. A., Stoopen G. M., van Muijen G. N., Kuznicki J., Ruiter D. J., Bloemers H. P. Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice. Cancer Res. 1992 Mar 1;52(5):1291–1296. [PubMed] [Google Scholar]
  27. Xie S., Luca M., Huang S., Gutman M., Reich R., Johnson J. P., Bar-Eli M. Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 1997 Jun 1;57(11):2295–2303. [PubMed] [Google Scholar]
  28. el-Deeb S., Thompson S. C., Covault J. Characterization of a cell surface adhesion molecule expressed by a subset of developing chick neurons. Dev Biol. 1992 Jan;149(1):213–227. doi: 10.1016/0012-1606(92)90278-o. [DOI] [PubMed] [Google Scholar]
  29. van Groningen J. J., Bloemers H. P., Swart G. W. 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. Cancer Res. 1995 Dec 15;55(24):6237–6243. [PubMed] [Google Scholar]
  30. van Groningen J. J., Egmond M. R., Bloemers H. P., Swart G. W. nmd, a novel gene differentially expressed in human melanoma cell lines, encodes a new atypical member of the enzyme family of lipases. FEBS Lett. 1997 Mar 3;404(1):82–86. doi: 10.1016/s0014-5793(97)00098-7. [DOI] [PubMed] [Google Scholar]
  31. van Muijen G. N., Jansen K. F., Cornelissen I. M., Smeets D. F., Beck J. L., Ruiter D. J. Establishment and characterization of a human melanoma cell line (MV3) which is highly metastatic in nude mice. Int J Cancer. 1991 Apr 22;48(1):85–91. doi: 10.1002/ijc.2910480116. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES