Summary
Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Over-expression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Edelman, GM: Cell adhesion molecules in the regulation of animal form and tissue pattern. Ann Rev Cell Biol 2: 81–116, 1986
Springer, TA: Adhesion receptors of the immune system. Nature 346: 425–434, 1990
Patarroyo, M, Makgoba, MW: Leukocyte adhesion to cells in immune and inflammatory responses. Lancet ii: 1139–1142, 1989
Williams, AF, Barclay, AN: The immunoglobulin superfamily-domains for cell surface recognition. Ann Rev Immunol 6: 381–405, 1988
Covault, J: Molecular biology of cell adhesion in neural development. In: Glover, DM, Hames, BD (eds) Molecular Neurobiology. IRL Press, Oxford, pp 143–200, 1989
Rutishauser, U, Jessel, TM: Cell adhesion molecules in vertebrate neural development. Physiol Rev 68: 819–857, 1988
Hoffman, S, Edelman, GM: Kinetics of homophilic binding by embryonic and adult forms of the neural cell adhesion molecule. Proc Natl Acad Sci USA 80: 5762–5766, 1983
Jaffe, SH, Froedlander, DR, Matsuzaki, F, Crossin, KL, Cunningham, BA, Edelman, GM: Differential effects of the cytoplasmic domains of cell adhesion molecules on cell aggregation and sorting out. Proc Natl Acad Sci USA 87: 3587–3593, 1990
Rutishauser, U, Acheson, A, Hall, AK, Sunshine, J: NCAM as a regulator of cell-cell interactions. Science 240: 53–57, 1988
Patel, K, Bourne, S, Phimister, B, Coakham, H, Kemshead, JT: Presence of neural cell adhesion molecule on human embryonic and brain tumors. Biochem Soc Trans 18: 408–410, 1990
Roth, J, Zuber, C, Wagner, P, Taatjes, DJ, Weisgerber, C, Heitz, PU, Goridis, C, Bitter-Suermann, D: Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. Proc Natl Acad Sci USA 85: 2999–3003, 1988
Thompson, J, Zimmermann, W: The carcinoembryonic antigen (CEA) gene family: structure, expression and evolution. Tumor Biol 9: 63–83, 1988
Benchimol, S, Fuks, A, Jothy, S, Beauchemin, N, Shirota, K, Stanners, CD: Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57: 327–334, 1989
Oikawa, S, Inuzuka, C, Kuroki, M, Matsuoka, Y, Kosati, G, Nakazato, H: Cell adhesion activity of nonspecific cross reactive antigen (NCA) and carcinoembryonic antigen (CEA) expressed on CHO cell surface: homophilic and heterophilic adhesion. Bioch Biophys Res Comm 164: 39–45, 1989
Wanebo, HJ, Rao, B, Pinsky, CM, Hoffman, RG, Stearns, M, Schwartz, MK, Oettgen, HF: Preopertive carcinoembryonic antigen level as a prognostic indicator in colorectal cancer. N Engl J Med 299: 448–451, 1978
Toth, CA, Rapoza, A, Kowal, A, Steele, G, Thomas, P: Receptor-mediated endocytosis by human Kupffer cells. Bioch Soc Trans 16: 1027–1028, 1988
Bryn, RA, Medrek, P, Thomas, P et al.: Effect of heterogeneity of carcinoembryonic antigen on liver cell membrane binding and its kinetics of removal from circulation. Cancer Res 45: 3137–3142, 1985
Jessup, JM, Giavazzi, R, Campbell, D, Cleary, K, Morikawa, K, Fidler, IJ: Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. Cancer Res 48: 1689–1692, 1988
Hostetter, RB, Augustus, LB, Mankarious, R, Chi, K, Fan, D, Toth, C, Thomas, P, Jessup, JM: Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. JNCI 82: 380–385, 1990
Farber, E, Cameron, R: The sequential analysis of cancer development. Adv Cancer Res 31: 125–226, 1980
Weinstein, IB: The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment. Cancer Res 48: 4135–4143, 1988
Vogelstein, B, Fearon, ER, Hamilton, SR, Kern, SE, Preisinger, AC, Leppert, M, Nakumura, Y, White, R, Smits, AMM, Bos, JL: Genetic alterations during colorectal-tumor development. N Engl J Med 319: 525–532, 1988
Lee, WH, Bookstein, R, Hong, F et al.: Human retinoblastoma susceptibility gene: cloning, identification and sequence. Science 235: 1394–1399, 1987
Fearon, ER, Cho, KR, Nigro, JM, Kern, SE, Simons, JW, Ruppert, JM, Hamilton, SR, Preisinger, AC, Thomas, G, Kinzler, KW, Vogelstein, B: Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247: 49–56, 1990
Fearon, ER, Vogelstein, B: A genetic model for colorectal tumorigenesis. Cell 61: 759–767, 1990
Clark, WH, Elder, DE, Guerry, DIV, Epstein, MN, Greene, MH, Horn, Mvan: A study of tumor progression. The precursor lesions of superficial spreading and nodular melanoma. Human Pathol 15: 1147–1165, 1984
Johnson, JP, Stade, BG, Rothbächer, U, Lehmann, JM, Riethmüller, G: Melanoma cell antigens and their association with malignant transformation and tumor progression. In: Ferrone, S (ed) Human Melanoma: Immunology, Diagnostics and Therapy. Springer Verlag, Berlin, pp 106–118, 1990
Lehmann, JM, Holzmann, B, Breitbart, EW, Schmiegelow, P, Riethmüller, G, Johnson, JP: Discrimination between benign and malignant cells of the melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. Cancer Res 47: 841–845, 1987
Sober, AJ: Prognostic factors for cutaneous melanoma. In: Ruiter, Welvaart, Ferrone, Cutaneous melanoma and precursor lesions, pp 126–142 (Nijhoff, Boston), 1984
Breslow, A: Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172: 902–908, 1970
Holzmann, B, Bröcker, EB, Lehmann, JM, Ruiter, DJ, Sorg, C, Riethmüller, G, Johnson, JP: Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes. Int J Cancer 39: 466–471, 1987
Lehmann, JM, Riethmüller, G, Johnson, JP: 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 USA 86: 9891–9895, 1989
Doyle, C, Strominger, JL: Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature 330: 256–259, 1987
Norment, AM, Salter, RD, Parham, P, Engelhard, VH, Littman, DR: Cell-cell adhesion mediated by CD8 and MHC class I molecules. Nature 336: 79–81, 1988
Smith, MEF, Marsh, SGE, Bodmer, JG, Gelsthorpek, K, Bodmer, WF: Loss of HLA-A, B, C allele products and lymphocyte function-associated antigen 3 in colorectal neoplasia. Pro Natl Acad Sci USA 86: 5557–5561, 1989
Esteban, F, Concha, A, Huelin, C, Perez-Ayala, M, Pedrinaci, S, Ruiz-Cabello, F, Garrido, F: Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx. Int J Cancer 43: 436–442, 1989
Gregory, CD, Murray, RJ, Edwards, CF, Rickinson, AB: Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med 167: 1811–1824, 1988
Natali, P, Nicotra, MR, Cavaliere, R, Bigotti, A, Romano, G, Temponi, M, Ferrone, S: Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions. Cancer Res 50: 1271–1278, 1990
Johnson, JP, Stade, BG, Holzmann, B, Schwäble, W, Riethmüller, G: De novo expression of cell adhesion molecule ICAM-1 in melanoma and increased risk of metastasis. Proc Natl Acad Sci 86: 641–644, 1989
Holzmann, B, Johnson, JP, Kaudewitz, P, Riethmüller, G: In situ analysis of antigens on malignant and benign cells of the melanocyte lineage: Differential expression of 2 surface molecules, gp 75 and gp 89. J Exp Med 161: 366–377, 1985
Johnson, JP, Stade, BG, Hupke, U, Holzmann, B, Riethmüller, G: The melanoma progression associated antigen P3.58 is identical to the intercellular adhesion molecule ICAM-1. Immunobiol 178: 275–284, 1988
Braakman, Goedegebuure, PS, Vreugdenhil, RJ, Segal, DM, Shaw, S, Bolhuis, RLH: ICAM-melanoma cells are relatively resistant to CD3- mediated T cell lysis. Int J Cancer 46: 475–480, 1990
Guerry, D, Alexander, MA, Zehngebot, L, Herlyn, M, Mitchell, KF, Zmijewski, CM: HLA-DR antigens permit human melanoma cells from early but not advanced disease to stimulate autologous lymphocytes. J Clin Invest 73: 267, 1984
Blood, CH, Zetter, BR: Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim et Biophys. Acta 1032: 89–118, 1990
Starkey, JR, Liggitt, HD, Jones, W, Hosick, HL: Influence of migratory blood cells on the attachment of tumor cells to vascular endothelium. Int J Cancer 34: 535–543, 1984
Aeed, PA, Nakajima, M, Welch, DR: The role of polymorphonuclear leukocytes (PMN) on the growth and metastatic potential of 13762NF mammary adenocarcinoma cells. Int J Cancer 42: 748–759, 1988
Cornil, I, Man, S, Fernandez, B, Kerbel, RS: Enhanced tumorigenicity, melanogenesis, and metastases of a human malignant melanoma after subdermal implantation in nude mice. JNCI 81: 938–944, 1989
Bankert, RB, Umemoto, T, Sugiyama, Y, Chen, FA, Repasky, E, Yokota, S: Human lung tumors, patients' peripheral blood lymphocytes and tumor infiltrating lymphocytes propagated in scid mice. Curr Top Microbiol Immunol 152: 201, 1989
Johnston, SC, Dustin, ML, Hibbs, ML, Springer, TA: On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. J Immunol 145: 1181–1187, 1990
Lipman, DJ, Pearson, WR: Rapid and sensitive protein similarity searches. Science 227: 1435–1439, 1985
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Johnson, J.P. Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. Cancer Metast Rev 10, 11–22 (1991). https://doi.org/10.1007/BF00046840
Issue Date:
DOI: https://doi.org/10.1007/BF00046840