Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 May 1;177(5):1257–1268. doi: 10.1084/jem.177.5.1257

Characterization of a novel Hodgkin cell line, HD-MyZ, with myelomonocytic features mimicking Hodgkin's disease in severe combined immunodeficient mice

PMCID: PMC2191008  PMID: 8386741

Abstract

A novel Hodgkin cell line, designated HD-MyZ, was established from the pleural effusion of a 29-yr-old patient with Hodgkin's disease (HD) of nodular sclerosing type. The majority of cells grow adherently and display typical morphological characteristics of Reed-Sternberg (RS) and Hodgkin (H) cells, i.e., large multi- and mononucleated cells with prominent nucleoli. Immunofluorescence analysis revealed a myelomonocytoid immunophenotype (expression of CD13 and CD68, and lack of lymphoid markers). HD-MyZ cells strongly expressed restin, a recently described intermediate filament-associated protein, the expression of which is restricted to H cells, RS cells, and in vitro cultivated peripheral blood monocytes. In addition mRNA expression of c- fms (colony-stimulating factor 1 receptor) could be induced in HD-MyZ cells by phorbol myristate acetate (PMA) stimulation. Southern blot analysis did not detect rearrangement of T cell receptor beta and immunoglobulin H loci, thus demonstrating the lack of lymphoid commitment. HD-MyZ cells were also devoid of Epstein-Barr virus genomes. HD-MyZ cells constitutively express mRNAs for interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-5, IL-6, IL-7, IL-8, IL-10, IL-1 receptor (type I), and IL-6 receptor. Stimulation of cells with PMA increased mRNA expression as well as the secretion of IL-1 beta, IL-6, and IL-8, and induced the de novo expression of IL-8 receptors. Xenotransplantation into severe combined immunodeficient (SCID) mice by intravenous or subcutaneous inoculation led to development of disseminated tumors with infiltrative and destructive growth. In addition lymphadenopathy, pleural effusion, and infiltration of spleen were observed. Morphological and immunological analysis of tumor cells revealed the same features as HD-MyZ cells. This cell line might be an important tool for understanding the pathogenesis and biology of HD. In addition the SCID mice model might prove helpful in developing new therapeutic strategies.

Full Text

The Full Text of this article is available as a PDF (5.2 MB).

Selected References

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

  1. Agnarsson B. A., Kadin M. E. The immunophenotype of Reed-Sternberg cells. A study of 50 cases of Hodgkin's disease using fixed frozen tissues. Cancer. 1989 Jun 1;63(11):2083–2087. doi: 10.1002/1097-0142(19890601)63:11<2083::aid-cncr2820631102>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  2. Azuma C., Tanabe T., Konishi M., Kinashi T., Noma T., Matsuda F., Yaoita Y., Takatsu K., Hammarström L., Smith C. I. Cloning of cDNA for human T-cell replacing factor (interleukin-5) and comparison with the murine homologue. Nucleic Acids Res. 1986 Nov 25;14(22):9149–9158. doi: 10.1093/nar/14.22.9149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  4. Bilbe G., Delabie J., Brüggen J., Richener H., Asselbergs F. A., Cerletti N., Sorg C., Odink K., Tarcsay L., Wiesendanger W. Restin: a novel intermediate filament-associated protein highly expressed in the Reed-Sternberg cells of Hodgkin's disease. EMBO J. 1992 Jun;11(6):2103–2113. doi: 10.1002/j.1460-2075.1992.tb05269.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  6. Chua A. O., Gubler U. Sequence of the cDNA for the human fibroblast type interleukin-1 receptor. Nucleic Acids Res. 1989 Dec 11;17(23):10114–10114. doi: 10.1093/nar/17.23.10114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cordingley F. T., Bianchi A., Hoffbrand A. V., Reittie J. E., Heslop H. E., Vyakarnam A., Turner M., Meager A., Brenner M. K. Tumour necrosis factor as an autocrine tumour growth factor for chronic B-cell malignancies. Lancet. 1988 Apr 30;1(8592):969–971. doi: 10.1016/s0140-6736(88)91782-5. [DOI] [PubMed] [Google Scholar]
  8. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  9. Cozzolino F., Rubartelli A., Aldinucci D., Sitia R., Torcia M., Shaw A., Di Guglielmo R. Interleukin 1 as an autocrine growth factor for acute myeloid leukemia cells. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2369–2373. doi: 10.1073/pnas.86.7.2369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Diehl V., Pfreundschuh M., Fonatsch C., Stein H., Falk M., Burrichter H., Schaadt M. Phenotypic and genotypic analysis of Hodgkin's disease derived cell lines: histopathological and clinical implications. Cancer Surv. 1985;4(2):399–419. [PubMed] [Google Scholar]
  11. Diehl V., von Kalle C., Fonatsch C., Tesch H., Jüecker M., Schaadt M. The cell of origin in Hodgkin's disease. Semin Oncol. 1990 Dec;17(6):660–672. [PubMed] [Google Scholar]
  12. Drexler H. G., Jones D. B., Diehl V., Minowada J. Is the Hodgkin cell a T- or B-lymphocyte? Recent evidence from geno- and immunophenotypic analysis and in-vitro cell lines. Hematol Oncol. 1989 Mar-Apr;7(2):95–113. doi: 10.1002/hon.2900070202. [DOI] [PubMed] [Google Scholar]
  13. Dörken B., Moldenhauer G., Pezzutto A., Schwartz R., Feller A., Kiesel S., Nadler L. M. HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes. J Immunol. 1986 Jun 15;136(12):4470–4479. [PubMed] [Google Scholar]
  14. Falk M. H., Tesch H., Stein H., Diehl V., Jones D. B., Fonatsch C., Bornkamm G. W. Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease. Int J Cancer. 1987 Aug 15;40(2):262–269. doi: 10.1002/ijc.2910400223. [DOI] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  16. Goodwin R. G., Friend D., Ziegler S. F., Jerzy R., Falk B. A., Gimpel S., Cosman D., Dower S. K., March C. J., Namen A. E. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell. 1990 Mar 23;60(6):941–951. doi: 10.1016/0092-8674(90)90342-c. [DOI] [PubMed] [Google Scholar]
  17. Goodwin R. G., Lupton S., Schmierer A., Hjerrild K. J., Jerzy R., Clevenger W., Gillis S., Cosman D., Namen A. E. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci U S A. 1989 Jan;86(1):302–306. doi: 10.1073/pnas.86.1.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gough N. M. Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem. 1988 Aug 15;173(1):93–95. doi: 10.1016/0003-2697(88)90164-9. [DOI] [PubMed] [Google Scholar]
  19. Gray P. W., Aggarwal B. B., Benton C. V., Bringman T. S., Henzel W. J., Jarrett J. A., Leung D. W., Moffat B., Ng P., Svedersky L. P. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984 Dec 20;312(5996):721–724. doi: 10.1038/312721a0. [DOI] [PubMed] [Google Scholar]
  20. Gruss H. J., Brach M. A., Drexler H. G., Bonifer R., Mertelsmann R. H., Herrmann F. Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. Cancer Res. 1992 Jun 15;52(12):3353–3360. [PubMed] [Google Scholar]
  21. Hall A., Brown R. Human N-ras: cDNA cloning and gene structure. Nucleic Acids Res. 1985 Jul 25;13(14):5255–5268. doi: 10.1093/nar/13.14.5255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holmes W. E., Lee J., Kuang W. J., Rice G. C., Wood W. I. Structure and functional expression of a human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1278–1280. doi: 10.1126/science.1840701. [DOI] [PubMed] [Google Scholar]
  23. Hsu S. M., Zhao X. Expression of interleukin-1 in Reed-Sternberg cells and neoplastic cells from true histiocytic malignancies. Am J Pathol. 1986 Nov;125(2):221–225. [PMC free article] [PubMed] [Google Scholar]
  24. Idzerda R. L., March C. J., Mosley B., Lyman S. D., Vanden Bos T., Gimpel S. D., Din W. S., Grabstein K. H., Widmer M. B., Park L. S. Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med. 1990 Mar 1;171(3):861–873. doi: 10.1084/jem.171.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jücker M., Abts H., Li W., Schindler R., Merz H., Günther A., von Kalle C., Schaadt M., Diamantstein T., Feller A. C. Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease. Blood. 1991 Jun 1;77(11):2413–2418. [PubMed] [Google Scholar]
  26. Jücker M., Schaadt M., Diehl V., Poppema S., Jones D., Tesch H. Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell lines. Hematol Oncol. 1990 Jul-Aug;8(4):191–204. doi: 10.1002/hon.2900080404. [DOI] [PubMed] [Google Scholar]
  27. Kadin M. E. Possible origin of the Reed-Sternberg cell from an interdigitating reticulum cell. Cancer Treat Rep. 1982 Apr;66(4):601–608. [PubMed] [Google Scholar]
  28. Kanzaki T., Kubonishi I., Eguchi T., Yano S., Sonobe H., Ohyashiki J. H., Ohyashiki K., Toyama K., Ohtsuki Y., Miyoshi I. Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin. Cancer. 1992 Feb 15;69(4):1034–1041. doi: 10.1002/1097-0142(19920215)69:4<1034::aid-cncr2820690434>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  29. Katamine S., Notario V., Rao C. D., Miki T., Cheah M. S., Tronick S. R., Robbins K. C. Primary structure of the human fgr proto-oncogene product p55c-fgr. Mol Cell Biol. 1988 Jan;8(1):259–266. doi: 10.1128/mcb.8.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kaufman D., Longo D. L. Hodgkin's disease. Crit Rev Oncol Hematol. 1992 Sep;13(2):135–187. doi: 10.1016/1040-8428(92)90021-h. [DOI] [PubMed] [Google Scholar]
  31. Lawrence J. B., Villnave C. A., Singer R. H. Sensitive, high-resolution chromatin and chromosome mapping in situ: presence and orientation of two closely integrated copies of EBV in a lymphoma line. Cell. 1988 Jan 15;52(1):51–61. doi: 10.1016/0092-8674(88)90530-2. [DOI] [PubMed] [Google Scholar]
  32. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  33. Loetscher H., Pan Y. C., Lahm H. W., Gentz R., Brockhaus M., Tabuchi H., Lesslauer W. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990 Apr 20;61(2):351–359. doi: 10.1016/0092-8674(90)90815-v. [DOI] [PubMed] [Google Scholar]
  34. Majello B., Kenyon L. C., Dalla-Favera R. Human c-myb protooncogene: nucleotide sequence of cDNA and organization of the genomic locus. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9636–9640. doi: 10.1073/pnas.83.24.9636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Maksem J. A., Hassan M. O., Carter J. R. The ultrastructural heterogeneity of the Reed-Sternberg cell and its resemblance to monocyte-macrophage differentiation in vivo. Ultrastruct Pathol. 1983 Jun;4(4):379–389. doi: 10.3109/01913128309140590. [DOI] [PubMed] [Google Scholar]
  36. Mukaida N., Shiroo M., Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366–1371. [PubMed] [Google Scholar]
  37. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nishida T., Nishino N., Takano M., Kawai K., Bando K., Masui Y., Nakai S., Hirai Y. cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line. Biochem Biophys Res Commun. 1987 Feb 27;143(1):345–352. doi: 10.1016/0006-291x(87)90671-1. [DOI] [PubMed] [Google Scholar]
  39. Olsson L., Behnke O. Phenotypic attributes of the malignant cell population in Hodgkin's disease indicate a monocyte/macrophage origin. Cancer Surv. 1985;4(2):421–438. [PubMed] [Google Scholar]
  40. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  41. Ponte P., Ng S. Y., Engel J., Gunning P., Kedes L. Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Res. 1984 Feb 10;12(3):1687–1696. doi: 10.1093/nar/12.3.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ravetch J. V., Siebenlist U., Korsmeyer S., Waldmann T., Leder P. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes. Cell. 1981 Dec;27(3 Pt 2):583–591. doi: 10.1016/0092-8674(81)90400-1. [DOI] [PubMed] [Google Scholar]
  43. Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
  44. Taniguchi T., Matsui H., Fujita T., Takaoka C., Kashima N., Yoshimoto R., Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983 Mar 24;302(5906):305–310. doi: 10.1038/302305a0. [DOI] [PubMed] [Google Scholar]
  45. Vieira P., de Waal-Malefyt R., Dang M. N., Johnson K. E., Kastelein R., Fiorentino D. F., deVries J. E., Roncarolo M. G., Mosmann T. R., Moore K. W. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. doi: 10.1073/pnas.88.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wang A. M., Doyle M. V., Mark D. F. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. doi: 10.1073/pnas.86.24.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Watt R., Stanton L. W., Marcu K. B., Gallo R. C., Croce C. M., Rovera G. Nucleotide sequence of cloned cDNA of human c-myc oncogene. Nature. 1983 Jun 23;303(5919):725–728. doi: 10.1038/303725a0. [DOI] [PubMed] [Google Scholar]
  48. Withers D. A., Harvey R. C., Faust J. B., Melnyk O., Carey K., Meeker T. C. Characterization of a candidate bcl-1 gene. Mol Cell Biol. 1991 Oct;11(10):4846–4853. doi: 10.1128/mcb.11.10.4846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wong G. G., Witek-Giannotti J., Hewick R. M., Clark S. C., Ogawa M. Interleukin 6: identification as a hematopoietic colony-stimulating factor. Behring Inst Mitt. 1988 Aug;(83):40–47. [PubMed] [Google Scholar]
  50. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  51. Wu J., Zhu J. Q., Han K. K., Zhu D. X. The role of the c-fms oncogene in the regulation of HL-60 cell differentiation. Oncogene. 1990 Jun;5(6):873–877. [PubMed] [Google Scholar]
  52. Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B., Taniguchi T., Hirano T., Kishimoto T. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988 Aug 12;241(4867):825–828. doi: 10.1126/science.3136546. [DOI] [PubMed] [Google Scholar]
  53. Yarden Y., Kuang W. J., Yang-Feng T., Coussens L., Munemitsu S., Dull T. J., Chen E., Schlessinger J., Francke U., Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. doi: 10.1002/j.1460-2075.1987.tb02655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Yokota T., Otsuka T., Mosmann T., Banchereau J., DeFrance T., Blanchard D., De Vries J. E., Lee F., Arai K. Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5894–5898. doi: 10.1073/pnas.83.16.5894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zakut-Houri R., Bienz-Tadmor B., Givol D., Oren M. Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. EMBO J. 1985 May;4(5):1251–1255. doi: 10.1002/j.1460-2075.1985.tb03768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES