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. 1990 Jan;136(1):181–189.

Lack of effect of colony-stimulating factors, interleukins, interferons, and tumor necrosis factor on the growth and differentiation of cultured Reed-Sternberg cells. Comparison with effects of phorbol ester and retinoic acid.

S M Hsu 1, P L Hsu 1
PMCID: PMC1877445  PMID: 1688689

Abstract

The neoplastic Hodgkin's Reed-Sternberg (H-RS) cells in Hodgkin's disease are surrounded in vivo by abundant reactive cells, the function of which may be attributed in part to their elaboration of various cytokines. Thus, a study of the interaction of H-RS cells with exogenous cytokines may provide information as to the mechanism of the clinical and histopathologic changes observed in Hodgkin's disease. This study examined the effect of various cytokines, and of phorbol ester (TPA) and retinoic acid, on the differentiation and proliferation of cultured H-RS cells (cell lines HDLM-1 and KM-H2). In addition, it was determined whether these cells were able to secrete cytokines after being treated with exogenous cytokines. The cytokines used included various types of interleukins (1, 2, and 3), colony-stimulating factors (GM, G, and M), interferons (alpha, beta, and gamma), and tumor necrosis factor (alpha). It was found that these cytokines, used alone or in combination, were not effective in modulating the proliferation and differentiation of cells, or the production of cytokines, in cultured H-RS cells. In contrast, this study revealed that retinoic acid can potentiate TPA-induced growth inhibition in cultured H-RS cells. Retinoic acid, when used alone, exhibited a minimal effect on cell differentiation. No synergistic effects of cytokines and retinoic acid on H-RS cells were observed. The failure of cultured H-RS cells to respond to exogenous cytokines suggests that, during the course of neoplastic transformation, of progression of disease, or of establishment of the cells in culture, H-RS cells lose their dependence on cytokines, although they retain the capacity to produce various cytokines.

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Selected References

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  1. Abita J. P., Gauville C., Balitrand N., Gespach C., Canivet J. Binding of 125I-insulin to the human histiocytic lymphoma cell line U-937: effect of differentiation with retinoic acid. Leuk Res. 1984;8(2):213–221. doi: 10.1016/0145-2126(84)90145-0. [DOI] [PubMed] [Google Scholar]
  2. Burrichter H., Heit W., Schaadt M., Kirchner H., Diehl V. Production of colony-stimulating factors by Hodgkin cell lines. Int J Cancer. 1983 Mar 15;31(3):269–274. doi: 10.1002/ijc.2910310303. [DOI] [PubMed] [Google Scholar]
  3. Byrne P. V., Heit W. F., March C. J. Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. Biochim Biophys Acta. 1986 Dec 12;874(3):266–273. doi: 10.1016/0167-4838(86)90025-7. [DOI] [PubMed] [Google Scholar]
  4. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Drexler H. G., Gaedicke G., Lok M. S., Diehl V., Minowada J. Hodgkin's disease derived cell lines HDLM-2 and L-428: comparison of morphology, immunological and isoenzyme profiles. Leuk Res. 1986;10(5):487–500. doi: 10.1016/0145-2126(86)90084-6. [DOI] [PubMed] [Google Scholar]
  6. Drexler H. G., Leber B. F., Norton J., Yaxley J., Tatsumi E., Hoffbrand A. V., Minowada J. Genotypes and immunophenotypes of Hodgkin's disease-derived cell lines. Leukemia. 1988 Jun;2(6):371–376. [PubMed] [Google Scholar]
  7. Goeddel D. V., Aggarwal B. B., Gray P. W., Leung D. W., Nedwin G. E., Palladino M. A., Patton J. S., Pennica D., Shepard H. M., Sugarman B. J. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):597–609. doi: 10.1101/sqb.1986.051.01.072. [DOI] [PubMed] [Google Scholar]
  8. Hecht T. T., Longo D. L., Cossman J., Bolen J. B., Hsu S. M., Israel M., Fisher R. I. Production and characterization of a monoclonal antibody that binds Reed-Sternberg cells. J Immunol. 1985 Jun;134(6):4231–4236. [PubMed] [Google Scholar]
  9. Herbst H., Tippelmann G., Anagnostopoulos I., Gerdes J., Schwarting R., Boehm T., Pileri S., Jones D. B., Stein H. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma: dissociation between phenotype and genotype. Leuk Res. 1989;13(2):103–116. doi: 10.1016/0145-2126(89)90134-3. [DOI] [PubMed] [Google Scholar]
  10. Ho C. K. Synergistic anticellular effect of a combination of beta-interferon and retinoic acid against U937 cells. Cancer Res. 1985 Nov;45(11 Pt 1):5348–5351. [PubMed] [Google Scholar]
  11. Hsu P. L., Hsu S. M. Production of tumor necrosis factor-alpha and lymphotoxin by cells of Hodgkin's neoplastic cell lines HDLM-1 and KM-H2. Am J Pathol. 1989 Oct;135(4):735–745. [PMC free article] [PubMed] [Google Scholar]
  12. Hsu S. M., Hsu P. L. Aberrant expression of T cell and B cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells. Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin for Hodgkin's Reed-Sternberg cells? Am J Pathol. 1989 Jan;134(1):203–212. [PMC free article] [PubMed] [Google Scholar]
  13. Hsu S. M., Hsu P. L., Lo S. S., Wu K. K. Expression of prostaglandin H synthase (cyclooxygenase) in Hodgkin's mononuclear and Reed-Sternberg cells. Functional resemblance between H-RS cells and histiocytes or interdigitating reticulum cells. Am J Pathol. 1988 Oct;133(1):5–12. [PMC free article] [PubMed] [Google Scholar]
  14. Hsu S. M., Hsu P. L. Phenotypes and phorbol ester-induced differentiation of human histiocytic lymphoma cell lines (U-937 and SU-DHL-1) and Reed-Sternberg cells. Am J Pathol. 1986 Feb;122(2):223–230. [PMC free article] [PubMed] [Google Scholar]
  15. Hsu S. M., Krupen K., Lachman L. B. Heterogeneity of interleukin 1 production in cultured Reed-Sternberg cell lines HDLM-1, HDLM-1d, and KM-H2. Am J Pathol. 1989 Jul;135(1):33–38. [PMC free article] [PubMed] [Google Scholar]
  16. Hsu S. M., Pescovitz M. D., Hsu P. L. Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. Blood. 1986 Jul;68(1):213–219. [PubMed] [Google Scholar]
  17. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  18. Hsu S. M., Soban E. Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem. 1982 Oct;30(10):1079–1082. doi: 10.1177/30.10.6182185. [DOI] [PubMed] [Google Scholar]
  19. Hsu S. M., Yang K., Jaffe E. S. Phenotypic expression of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease. Am J Pathol. 1985 Feb;118(2):209–217. [PMC free article] [PubMed] [Google Scholar]
  20. Hsu S. M., Zhao X., Chakraborty S., Liu Y. F., Whang-Peng J., Lok M. S., Fukuhara S. Reed-Sternberg cells in Hodgkin's cell lines HDLM, L-428, and KM-H2 are not actively replicating: lack of bromodeoxyuridine uptake by multinuclear cells in culture. Blood. 1988 May;71(5):1382–1389. [PubMed] [Google Scholar]
  21. 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]
  22. Hsu S. M., Zhao X., Hsu P. L., Lok M. S. Extracellular matrix does not induce the proliferation, but promotes the differentiation, of Hodgkin's cell line HDLM-1. Am J Pathol. 1987 Apr;127(1):9–14. [PMC free article] [PubMed] [Google Scholar]
  23. Kamesaki H., Fukuhara S., Tatsumi E., Uchino H., Yamabe H., Miwa H., Shirakawa S., Hatanaka M., Honjo T. Cytochemical, immunologic, chromosomal, and molecular genetic analysis of a novel cell line derived from Hodgkin's disease. Blood. 1986 Jul;68(1):285–292. [PubMed] [Google Scholar]
  24. Kaye J., Janeway C. A., Jr Induction of receptors for interleukin 2 requires T cell Ag:Ia receptor crosslinking and interleukin 1. Lymphokine Res. 1984 Summer;3(4):175–182. [PubMed] [Google Scholar]
  25. Koeffler H. P., Ranyard J., Yelton L., Billing R., Bohman R. Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4080–4084. doi: 10.1073/pnas.81.13.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Last-Barney K., Homon C. A., Faanes R. B., Merluzzi V. J. Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1. J Immunol. 1988 Jul 15;141(2):527–530. [PubMed] [Google Scholar]
  27. Lippman S. M., Kessler J. F., Meyskens F. L., Jr Retinoids as preventive and therapeutic anticancer agents (Part I). Cancer Treat Rep. 1987 Apr;71(4):391–405. [PubMed] [Google Scholar]
  28. Munker R., Koeffler P. In vitro action of tumor necrosis factor on myeloid leukemia cells. Blood. 1987 Apr;69(4):1102–1108. [PubMed] [Google Scholar]
  29. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Newcom S. R., O'Rourke L. Potentiation of fibroblast growth by nodular sclerosing Hodgkin's disease cell cultures. Blood. 1982 Jul;60(1):228–237. [PubMed] [Google Scholar]
  31. Olsson I. L., Breitman T. R., Gallo R. C. Priming of human myeloid leukemic cell lines HL-60 and U-937 with retinoic acid for differentiation effects of cyclic adenosine 3':5'-monophosphate-inducing agents and a T-lymphocyte-derived differentiation factor. Cancer Res. 1982 Oct;42(10):3928–3933. [PubMed] [Google Scholar]
  32. Olsson I. L., Breitman T. R. Induction of differentiation of the human histiocytic lymphoma cell line U-937 by retinoic acid and cyclic adenosine 3':5'-monophosphate-inducing agents. Cancer Res. 1982 Oct;42(10):3924–3927. [PubMed] [Google Scholar]
  33. Rubin B. Y., Anderson S. L., Lunn R. M., Richardson N. K., Hellermann G. R., Smith L. J., Old L. J. Tumor necrosis factor and IFN induce a common set of proteins. J Immunol. 1988 Aug 15;141(4):1180–1184. [PubMed] [Google Scholar]
  34. Schwab U., Stein H., Gerdes J., Lemke H., Kirchner H., Schaadt M., Diehl V. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid cells. Nature. 1982 Sep 2;299(5878):65–67. doi: 10.1038/299065a0. [DOI] [PubMed] [Google Scholar]
  35. Trinchieri G., Rosen M., Perussia B. Retinoic acid cooperates with tumor necrosis factor and immune interferon in inducing differentiation and growth inhibition of the human promyelocytic leukemic cell line HL-60. Blood. 1987 Apr;69(4):1218–1224. [PubMed] [Google Scholar]
  36. Zhang Y. H., Lin J. X., Yip Y. K., Vilcek J. Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6802–6805. doi: 10.1073/pnas.85.18.6802. [DOI] [PMC free article] [PubMed] [Google Scholar]

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