Summary
The Epstein-Barr virus (EBV)-encoded membrane protein, LMP, is expressed in a proportion of undifferentiated nasopharyngeal carcinomas (NPC). Previous studies have shown that the transfection of the gene encoding LMP into a human keratinocyte line, RHEK-1, induces morphological alterations and a reduced expression of cytokeratins. We have analyzed immunophenotypic changes in the RHEK-1 line following LMP-transfection and compared these changes with the phenotype of NPC biopsies. We demonstrate a downregulation of two epithelial markers, an epithelial glycoprotein (EGP) defined by the monoclonal antibody Ber-EP4 and the epithelial membrane antigen (EMA). Furthermore, a lymphocyte activation-associated antigen, CDw70 antigen, which was absent from the parental line was expressed in virtually all LMP-transfected cells, whereas no similar effect was seen with respect to the CD30 activation antigen.
Nine EBV-positive human NPCs, six of which were LMP-positive expressed the EGP and EMA. The CDw70 antigen, which is not normally present in epithelial cells, was expressed in eight biopsies, whereas the CD30 antigen was not detectable. Our findings are in keeping with the notion that LMP expression may contribute to the immunophenotype of human NPCs.
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Cordell J, Richardson TC, Pulford KAF, Ghosh AK, Gatter KC, Heyderman E, Mason DY (1985) Production of monoclonal antibodies against human epithelial membrane antigen for use in diagnostic immunocytochemistry. Br J Cancer 52:347–354
Dawson CW, Rickinson AB, Young LS (1990) Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature 344:777–780
Delsol G, Gatter KC, Stein H, Erber WN, Pulford KAF, Zinne K, Mason DY (1984) Human lymphoid cells express epithelial membrane antigen. Lancet 2:1124–1129
Fahraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G, Falk K, Nilsson E, Yadav M, Busson P, Tursz T, Kallin B (1988) Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer 42:329–338
Fahraeus R, Rymo L, Rhim JS, Klein G (1990) Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature 345:447–449
Hanto DW, Frizzera G, Purtilo DT, Sakamoto K, Sullivan JL, Saemundsen AK, Klein G, Simmons RL, Najarian JS (1981) Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Cancer Res 41:4253–4261
Herbst H, Niedobitek G, Kneba M, Hummel M, Finn T, Anagnostopoulos I, Bergholz M, Krieger G, Stein H (1990) High incidence of Epstein-Barr virus genomes in Hodgkin’s disease. Am J Pathol 137:13–18
Heyderman E, Strudley I, Powell G, Richardson TC, Cordell JC, Mason DY (1985) A new monoclonal antibody to epithelial membrane antigen (EMA)-E29. A comparison of its immunocytochemical reactivity with polyclonal anti-EMA antibodies and with another monoclonal antibody, HMFG-2. Br J Cancer 52:355–361
Kieff E, Liebowitz D (1990) Epstein-Barr virus and its replication. In: Fields BN, Knipe DM (eds) Virology. Raven Press, New York, pp 1889–1920
Klein G, Giovanella BC, Lindahl T, Fialkow PJ, Singh S, Stehlin JS (1974) Direct evidence for the presence of Epstein-Barr virus DNA and nuclear antigen in malignant epithelial cells from patients with poorly differentiated carcinoma of the nasopharynx. Proc Natl Acad Sci USA 71:4737–4741
Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H (1990) Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelia. J Clin Pathol 43:213–219
Niedobitek G, Hansmann ML, Herbst H, Young LS, Dienemann D, Hartmann CA, Finn T, Pitteroff S, Welt A, Anagnostopoulos I, Friedrich R, Lobeck H, Sam CK, Araujo I, Rickinson AB, Stein H (1991) Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol 165:17–24
Niedobitek G, Young LS, Sam CK, Brooks L, Prasad U, Rickinson AB (1992) Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas. Am J Pathol (in press)
Polack A, Hartl G, Zimber U, Freese UK, Laux G, Takaki K, Hohn B, Gissmann L, Bornkamm GW (1984) A complete set of overlapping cosmid clones of M-ABA virus derived from nasopharyngeal carcinoma and its similarity to other EpsteinBarr virus isolates. Gene 27:279–288
Rooney CM, Gregory CD, Rowe M, Finerty S, Edwards C, Rupani H, Rickinson AB (1986) Endemic Burkitt’s lymphoma: phenotypic analysis of tumor biopsy cells and derived tumor cell lines. J Natl Cancer Inst 77:681–687
Rowe M, Evans HS, Young LS, Hennessy K, Kieff E, Rickinson AB (1987a) Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells. J Gen Virol 68:1575–1586
Rowe M, Rowe DT, Gregory CD, Young LS, Farrell PJ, Rupani H, Rickinson AB (1987b) Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt’s lymphoma cells. EMBO J 6:2743–2751
Rüger R, Bornkamm GW, Fleckenstein B (1984) Human cytomegalovirus DNA sequences with homology to the nuclear genome. J Gen Virol 65:1351–1364
Schwarting R, Gerdes J, Dürkop H, Falini B, Pileri S, Stein H (1989) Ber-H2: A new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood 74:1678–1689
Simon B, Podolsky DK, Moldenhauer G, Isselbacher KJ, Gattoni-Celli S, Brand SJ (1990) Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein. Proc Natl Acad Sci USA 87:2755–2759
Stein H, Gatter K, Asbahr H, Mason DY (1985) Use of freeze-dried paraffin-embedded sections for immunohistologic staining with monoclonal antibodies. Lab Invest 52:676–683
Stein H, Schwarting R, Niedobitek G, Dallenbach F (1989) Cluster report: CDw70. In: Knapp W, Dörken B, Gilks WR, Rieber EP, Schmidt RE, Stein H, von dem Borne AEGK (eds) Leucocyte typing IV. Oxford University Press, Oxford, pp 446–449
Wang D, Liebowitz D, Kieff E (1985) An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 43:831–840
Wang D, Liebowitz D, Wang F, Gregory C, Rickinson A, Larson R, Springer T, Kieff E (1988) Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity. J Virol 62:4173–4184
Wang F, Gregory C, Sample C, Rowe M, Liebowitz D, Murray R, Rickinson A, Kieff E (1990) Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3 c are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 64:2309–2318
Wolf H, Zur Hausen H, Becker V (1973) EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nature 244:245–247
Young LS, Dawson CW, Clark D, Rupani H, Busson P, Tursz T, Johnson A, Rickinson AB (1988) Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol 69:1051–1065
Zur Hausen H, Schulte-Holthausen H, Klein G, Henle W, Henle G, Clifford P, Santesson L (1970) EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature 228:1056–1058
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Niedobitek, G., Fahraeus, R., Herbst, H. et al. The Epstein-Barr virus encoded membrane protein (LMP) induces phenotypic changes in epithelial cells. Virchows Archiv B Cell Pathol 62, 55–59 (1992). https://doi.org/10.1007/BF02899665
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DOI: https://doi.org/10.1007/BF02899665