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. 1998 Oct;18(5):497–507. doi: 10.1023/A:1026327309345

Interferon Yield and MHC Antigen Expression of Human Medulloblastoma Cells and Its Suppression During Dibutyryl Cyclic AMP-Induced Differentiation: Do Medulloblastoma Cells Derive from Bipotent Neuronal and Glial Progenitors?

Kae Chang Park 1, Keiji Shimizu 3, Toru Hayakawa 3
PMCID: PMC11560147  PMID: 9777250

Abstract

1. Human medulloblastoma (ONS-76), a central nervous system (CNS)-derived undifferentiated cell line, was found to possess glial characteristics as defined by responses in the interferon (IFN) system; ONS-76 cells produced as much IFN-β as human fibroblast and glioma cells by viral infection and poly(I):poly(C) induction.

2. Major histocompatibility complex (MHC) class I antigens were also induced under IFN-β stimulation. ONS-76 cells expressed neurofilament protein, as shown by Northern blot analysis, and morphological differentiation was induced by dibutyryl cyclic AMP (dcAMP).

3. Expression of IFN-β and MHC class I antigens was suppressed in ONS-76 cells during the dcAMP-induced differentiation.

4. These results showed that ONS-76 cells possessed a glial properly in IFN system responses and a neuronal property in cytoskeleton protein, suggesting that the precursors of medulloblastoma may be characterized as bipotent neuronal and glial progenitors in CNS.

Keywords: medulloblastoma, CNS, interferon, differentiation

REFERENCES

  1. Bailey, P., and Cushing, H. (1925). Medulloblastoma cerebelli; A common type of midcerebellar glioma of childhood. Arch. Neurol. Psychiat.14:192–224. [Google Scholar]
  2. Barlow, D. C., Randle, C. F., and Burke, D. C. (1984). Interferon synthesis in the early post-implantation mouse embryo. Differentiation27:229–235. [DOI] [PubMed] [Google Scholar]
  3. Cathala, F., and Baron, S. (1970). Interferon in rabbit brain, cerebrospinal fluid and serum following administration of polyinosinic-polycytidylic acid. J. Virol.14:1355–1358. [PubMed] [Google Scholar]
  4. Chader, G. J. (1987). Multipotential differentiation of human Y-19 retinoblastoma cells in attachment culture. Cell Different. 20:209–216. [DOI] [PubMed] [Google Scholar]
  5. Church, G. M., and Gilbert, W. (1984). Genomic sequencing. Proc. Natl. Acad. Sci. USA81:1991–1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Francis, M. K., and Lehman, J. M. (1989). Control of beta-interferon expression in murine embryonic carcinoma F9 cells. Mol. Cell Biol.9:3553–3556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Friedman, H. S., Burger, P. C., Bigner, S. H., Trojanowski, J. Q., Wikstrand, C. J., Halperin, E. C., and Bigner, D. D. (1985). Establishment and characterization of the medulloblastoma cell line and transplantable xenograft D283. Med. J. Neuropathol. Exp. Neurol.44:592–605. [DOI] [PubMed] [Google Scholar]
  8. Friedman, H. S., Burger, P. C., Bigner, S. H., Trojanowski, J. Q., Brodeur, G. M., He, X., Wikstrand, C. J., Kurtzberg, J., Beren, M. E., Halperin, E. C., and Bigner, D. D. (1988). Phenotypic and genotypic analysis of a human medulloblastoma cell line and transplantable xenograft (D341 Med) demonstrating amplification of c-myc. Am. J. Pathol.130:472–484. [PMC free article] [PubMed] [Google Scholar]
  9. Fujita, T., and Kohno, S. (1981). Studies on interferon priming: Cellular response to viral and nonviral inducers and requirement of protein synthesis. Virology112:62–69. [DOI] [PubMed] [Google Scholar]
  10. Fujita, T., Ohno, S., Yasumitsu, H., and Taniguchi, T. (1985). Delimitation and properties of DNA sequences required for the regulated expression of human interferon-β gene. Cell41:489–496. [DOI] [PubMed] [Google Scholar]
  11. Gage, F. H., Jasodhara, R., and Fisher, L. J. (1995). Isolation, characterization, and use of stem cells from the CNS. Annu. Rev. Neurosci.18:159–192. [DOI] [PubMed] [Google Scholar]
  12. Harada, H., Fujita, T., Miyamoto, M., Kimura, Y., Maruyama, M., Furia, A., Miyata, T., and Taniguchi, T. (1989). Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell58:729–739. [DOI] [PubMed] [Google Scholar]
  13. Harada, H., Willison, K., Sakakibara, J., Miyamoto, M., Fujita, T., and Taniguchi, T. (1990). Absence of the type 1 IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell63:303–312. [DOI] [PubMed] [Google Scholar]
  14. Harada, H., Kitagawa, M., Tanaka, N., Yamamoto, H., Harada, K., Ishihara, M., and Taniguchi, T. (1993). Anti-oncogenic and oncogenic of potentials interferon regulatory factor-1 and-2. Science259:971–974. [DOI] [PubMed] [Google Scholar]
  15. Hogan, B., Beddington Rosa., Constantini, F., and Lacy, E. (1994). Manipulating the Mouse Embryo, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. [Google Scholar]
  16. Jacobsen, P. F., Jenkyn, D. J., and Paradimittriou, J. M. (1985). Establishment of a human medulloblastoma cell line and its heterotransplantation into nude mice. J. Neuropathol. Exp. Neurol.44:472–485. [DOI] [PubMed] [Google Scholar]
  17. Larsson, I., Landstrom, L. E., Larner, E., Lundgrem, E., Miorner, H., and Strannegard, L. (1989). Interferon production in glia and glioma cell lines. Interferon Immun.22:786–789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lendahl, U., Zimmerman, L. B., and MacKey, R. D. G. (1990). CNS stem cells express a new class of intermediate filament protein. Cell60:585–595. [DOI] [PubMed] [Google Scholar]
  19. Lieberman, A. P., Pitha, P. M., Shin, H. S., and Shin, M. L. (1989). Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotrophic virus. Proc. Natl. Acad. Sci. USA86:6348–6352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miyamoto, M., Fujita, T., Kimura, Y., Maruyama, M., Harada, H., Sudo, Y., Miyata, T., and Taniguchi, T. (1988). Regulated expression of a gene encoding a nuclear factor, IRF-1, that specially binds to IFN-β gene regulatory elements. Cell54:903–913. [DOI] [PubMed] [Google Scholar]
  21. Myers, M. W., Lazzarini, R. A., Lee, V. M. Y., Schlaepfer, W. W., and Nelson, D. L. (1987). The human mid-size neurofilament submit: A repeated protein sequence and the relationship of its gene to the intermediate filament gene family. EMBO J.6:1617–1626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ozato, K., Wan, Y.-J., and Orrison, B. M. (1985). Mouse major histocompatibility class I gene expression begins at midsomite stage and is inducible in earlier-stage embryos by interferon. Proc. Natl. Acad. Sci. USA82:2427–2431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Prasad, K. N., and Hsie, A. W. (1971). Morphological differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3′:5′-cyclic monophosphate. Nature233:141–142. [DOI] [PubMed] [Google Scholar]
  24. Pulver, M., Carrel, S., Mach, J. P., and de Tribolet, N. (1987). Cultured human fetal astrocytes can be induced by interferon-β to express HLA-DR. J. Neuroimmunol.14:123–133. [DOI] [PubMed] [Google Scholar]
  25. Rubinstein, L. J. (1975). The cerebellar medulloblastoma: Its origin, differentiation, morphological variants and biological behavior. In Handbook of Clinical Neurology, New York, pp. 167–193.
  26. Russel, D. S., and Rubinstein, L. J. (1989). Pathology of Tumours of the Nervous System, Williams & Wilkins, Baltimore, pp. 251–279. [Google Scholar]
  27. Schubert, D. (1986). Developmental Biology of Cultured Nerve, Muscle, and Glia, John Wiley and Sons, New York, pp. 122–130. [Google Scholar]
  28. Stemple, D. L., and Anderson, D. J. (1992). Isolation of a stem cell for neurons and glia from the mammalian neuronal crest. Cell71:973–985. [DOI] [PubMed] [Google Scholar]
  29. Stewart, W. E., and Sulkin, S. E. (1966). Interferon production in hamsters experimentally infected with rabies virus. Proc. Soc. Exp. Biol. Med.123:650–653. [DOI] [PubMed] [Google Scholar]
  30. Strickland, S., Smith, K. K., and Marotti, K. R. (1980). Hormonal induction of differentiation in teratocarcinoma stem cell: Generation of parental endoderm by retinoic acid and dibutyl cAMP. Cell21:347–355. [DOI] [PubMed] [Google Scholar]
  31. Tamura, K., Shimizu, K., Yamada, M., Okamoto, Y., Matsui, Y., Park, K.-C., Mabuchi, E., Moriuchi, S., and Mogami, H. (1989). Expression of major histocompatibility complex on human medulloblastoma cells with neuronal differentiation. Cancer Res.49:5380–5384. [PubMed] [Google Scholar]
  32. Tamura, T., Ishihara, M., Lamphier, M. C., Tanaka, N., Oishi, I., Aizawa, S., Matsuyama, T., Mak, T. W., Taki, S., and Taniguchi, T. (1995). An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. Nature376:596–599. [DOI] [PubMed] [Google Scholar]
  33. Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M. S., Aizawa, S., Mak, T. W., and Taniguchi, T. (1994). Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell77:829–839. [DOI] [PubMed] [Google Scholar]
  34. Taniguchi, T. (1988): Regulation of cytokine gene expression. Annu. Rev. Immunol.6:439–464. [DOI] [PubMed] [Google Scholar]
  35. Taylor, M., and Reh, T. A. (1989) Induction of differentiation of rat retinal, germinal, neuroepithelial cells by dbcAMP. J. Neurobiol.21:470–481. [DOI] [PubMed] [Google Scholar]
  36. Tedeschi, B., Barrett, J. N., and Keane, R.W. (1986). Astrocytes produce interferon that enhances the expression of H-2 antigens on a subpopulation of brain cells. J. Cell Biol.102:2244–2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Temple, S. (1989). Division and differentiation of isolated CNS blast cells in microculture. Nature340:471–473. [DOI] [PubMed] [Google Scholar]
  38. Thomas, P. S. (1980). Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA77:5201–5205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Valtz, N. L. M., Hayes, T. E., Norregaard, T., Liu, S., and Mckay, R. D. G. (1991). An embryonic origin for medulloblastoma. New Biol.3:364–371. [PubMed] [Google Scholar]
  40. Wong, G. H. W., Bartlett, P. F., Clark-Lewis, I., Battye, F., and Schrader, J. W. (1984). Inducible expression of H-2 and Ia antigens on brain cells. Nature310:688–691. [DOI] [PubMed] [Google Scholar]
  41. Yamada, M., Shimizu, K., Tamura, K., Okamoto, Y., Matsui, Y., Moriuchi, S., Park, K.-C., Mabuchi, E., Yamamoto, K., Hayakawa, T., and Mogami, H. (1989). Establishment and biological characterization of human medulloblastoma cell lines. Brain Nerve41:695–702. [PubMed] [Google Scholar]

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