Summary
Four in vitro cell lines (L 428, L 439, L 538, and L 540) were established from different materials of three patients with Hodgkin's disease: pleural effusions, peripheral blood, and bone marrow. The histological diagnosis was confirmed in all cases by several independent histologists. All four cell lines have been in culture for over 6 months up to over 3 years. The neoplastic nature of the culture cells is indicated by the demonstration of several structural and numeric chromosome abnormalities associated with a monoclonal pattern of marker chromosomes. EBV-specific antigens (EBNA, VCA) were not detected in either cell line. Ia-like antigens, receptors for human T cells, acid phosphatase, and acid esterase were shown to be present in the cultured cells. All cell lines lacked surface or cytoplasmic Ig, HTLA, receptors for C3b, C3d, IgG-Fc, mouse E or sheep E, and were devoid of lysozyme, peroxidase, and chloracetate esterase. The described features do not represent B cells, T cells, myeloid cells, monocytes, or macrophages. The morphology and the marker pattern of the culture cells, however, is identical with that of freshly obtained Hodgkin's (H)- and Sternberg-Reed (SR)-cells, except for the lack of CIg in the in vitro cells, which is explained by the culture conditions. Heterotransplantation in nude mice was achieved by intracranial inoculation and by s.c. transplantation of cultured cells embedded in a plasma clot. The described findings suggest that these cultured Hodgkin's cell lines are indeed derived from H and SR cells. The cellular origin of these cells is not clear, the loss of cellular differential markers during the process of possible dedifferentiation is discussed.
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References
Biniaminov M, Ramot B (1974) Possible T-lymphocyte origin of Reed-Sternberg cells. Lancet I:368
Diehl V, Krause P, Hellriegel KP, Busche M, Schedel J, Laskewitz E (1977) Lymphoid cell lines: in vitro cell markers in correlation to tumorigenicity in nude mice. Haematol Bloodtransfus 20:
Dorfmann RF, Rice DF, Mitchel AD, Kempson RL, Levine G (1973) Ultrastructural studies of Hodgkin's disease. Nat Cancer Inst Monogr 36:221–238
Giovanella B, Nilsson K, Zech L, Yim O, Klein G, Stehlin JS (1979) Growth of diploid, Epstein-Barr virus carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions. Int J Cancer 24:103–113
Glick AD, Leech JH, Flexner JM, Collins RD (1976) Ultrastructural study of Reed-Sternberg cells. Am J Pathol 85:195–200
Graham RC, Karnovsky MJ (1965) Histochemical demonstration of monoamine oxidase activity by coupled peroxidase oxidation. J Histochem Cytochem 13:604–605
Henle G, Henle W (1966) Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol 91:1248–1256
Kadin ME, Asbury AK (1973) Long term cultures of Hodgkin's disease. A morphologic and radiographic study. Lab Invest 18:181–184
Kadin ME, Billing RJ (1978) B-lymphocyte antigens in the differential diagnosis of human neoplasia. Blood 15 (5):813–823
Kaplan HS, Gartner S (1977) “Sternberg-Reed” giant cells of Hodgkin's disease: Cultivation in vitro, heterotransplantation and characterization as neoplastic macrophages. Int J Cancer 19:511–525 (1977)
Leder LD (1967) Die fermentcytochemische Erkennung normaler und neoplastischer Erythropoesezellen in Schnitt und Austrich. Blut 15:289–293
Leech H (1973) Immunoglobulin-positive Reed-Sternberg cells in Hodgkin's disease. Lancet 2:265–266
Lozzio BB, Lozzio CB, Machado E (1976) Brief communication: human myelogenous (PH 1+) leukemia cell line: transplantation into athymic nude mice. J Natl Cancer Inst 56: 627–629
Mori Y, Lennert K (1969) Electron microscopic atlas of lymph node cytology and pathology. Springer, Berlin Heidelberg New York, pp 29–30
Nilsson K, Giovanella BC, Stehlin JS, Klein G: Tumorigenicity of human hematopoetic cell lines in athymic nude mice. Int J Cancer 19:337–344
Papadimitriou CS, Stein H, Lennert K (1978) The complexity of immunohistochemical staining pattern of Hodgkin's and Sternberg-Reed cells-demonstration of immunoglobulin albumin, α1-antichymotrypsin and lysozyme. Int J Cancer 21:531–541
Payne SV, Jones DB, Wright DH (1977) Reed-Sternberg cell/lymphocyte interaction. Lancet 180: 768–769
Rappaport H (1966) Tumors of the hematopoietic system: In: Atlas of tumor pathology, Sect. 3, Fasc. 8. Armed Forces Institute of Pathology, Washington DC
Reedman BM, Klein G (1973) Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and nonproducer lymphoblastoid cell lines. Int J Cancer 11:499–520
Schaadt M, Kechner H, Fonatsch C, Diehl V (1979) Intracranial heterotransplantation of human hematopoetic cells in nude mice. In J Cancer 23:751–761
Stein H, Papadimitriou CS, Bovman H, Lenert K, Fuchs J (1978a) Demonstration of immunoglobulin production by tumor cells in non-Hodgkin's and Hodgkin's malignant lymphomas and its significance for their classification. Recent Results in Cancer Res 158–175
Stein H, Siemssen U, Lennert K (1978b) Complement receptor subtypes C3b and C3d in lymphatic tissue and follicular lymphoma. Br J Cancer 37:520–529
Sumner AT, Evans HJ, Huckland RA (1971) New technique for distinguishing between human chromosomes. Nature 232:31–32
Thoenes J, Stein H (1979) Prosperties of an Fcy-binding protein isolated from human leukemic B cells. J Exp Med 150:1049–1066
Tolksdorf G, Stein H (1979) Acid alpha-naphtyl acetate esterase in hairycell leukemia cells and other cells of the hematopoetic system. Blut 39:165–176
Tolksdorf G, Stein H, Lennert K (1980) Morphological and immunological definition of a malignant lymphoma derived from germinal-centre cells with cleaved nuclei (centrocytes). Br J Cancer 41:168–182
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Supported by the Deutsche Forschungsgemeinschaft Bonn/Bad Godesberg, grant nos. Di 184/6 and SFB 111/D8
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Diehl, V., Kirchner, H.H., Schaadt, M. et al. Hodgkin's disease: Establishment and characterization of four in vitro cell lines. J Cancer Res Clin Oncol 101, 111–124 (1981). https://doi.org/10.1007/BF00405072
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DOI: https://doi.org/10.1007/BF00405072