The Interaction Between Cytokines and Growth Factors on the Growth of Glioma Cells

  • Jun Yoshida
  • Toshihiko Wakabayashi
  • Masaaki Mizuno
  • Hirofumi Oyama
  • Kyoko Nehashi
  • Kenichiro Sugita


There are several cytokines and growth factors which are related to the autocrine or paracrine growth of human glioma cells. Platelet-derived growth factor (PDGF) [1], insulin-like growth factor-II (IGF-II) [2], tumor necrosis factor-α (TNF-α), interferon-β (IFN-β) [3], and transforming growth factor-β (TGF-β) [4] have been reported to be synthesized from human glioma cells and released by a variety of forms of induction; they are believed to stimulate or inhibit the growth of glioma cells themselves. On the other hand, IFN and TNF were proved to have a direct anti-proliferative activity against glioma cells in vitro [5–7] and in vivo [5,6], and both cytokines were used clinically for the treatment of patients with malignant glioma [5]. The high dose of 1–3 × 106 IFN-β or of 1–5 × 105 TNF-α is usually administered intravenously, intra-arterially, and/or intrathecally. The results show that a regression of tumor was definitely demonstrated in some cases, although the response rate was not very high, while a reversed progression of tumor was also encountered in a few cases. In order to analyze the mechanism of exogenously added cytokines on growth regulation of human glioma cells, we examined the effect of IFN-β and TNF-α on human glioma cell lines in vitro, and studied the interaction between the growth factors PDGF, IGF-II, and TGF-β.


Glioma Cell Malignant Glioma Glioma Cell Line Human Glioma Cell Human Glioma Cell Line 
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  1. 1.
    Nister M, Heldin CH, Westermark B (1986) Clonal variation of a platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma. Cancer Res 46: 332–340PubMedGoogle Scholar
  2. 2.
    Yoshida J, Inoue I, Mizuno M, Oyama H, Nehashi K, Sugita K (1989) Production of HuIFN-β and IGF-II from human glioma cell lines. Neurological Res (Japan) 2: 159–164Google Scholar
  3. 3.
    Larsson I, Landstrom LE, Larner E, Lundgren E, Miorner H, Strannegard O (1987) Interferon production in glia and glioma cell lines. Infect Immun 22: 786–789Google Scholar
  4. 4.
    Clark WC, Bressler J (1988) Transforming growth factor-b-like activity in tumors of the central nervous system. J Neurosurg 67: 920–924Google Scholar
  5. 5.
    Yoshida J, Kato K, Wakabayashi T, Enomoto H, Inoue I, Kageyama N (1986) Antitumor activity of interferon-b against malignant glioma in combination with chemotherapeutic agent of nitrosourea (ACNU). In: Cantell K, Schellekens (eds) The biology of the interferon system. Martinus Nijhoff, Boston, pp 399–406Google Scholar
  6. 6.
    Enomoto H, Yoshida J, Kageyama N, Ueda R, Kato T, Ota (1986) Anti-tumor activity of human recombinant TNF against human malignant glioma cell lines and combination effect with HuIFN-β. Gan To Kakagu Ryoho (Jpn J Cancer Chemotherap) 13: 1953–1961Google Scholar
  7. 7.
    Rutka J, Giblin JR, Berens ME, Bar-Shiva E, Tokuda K, McCulloch JR, Rosenblum ML, Eessalu TE, Aggarwal BB, Bodel WJ (1988) The effect of human recombinant tumor necrosis factor on glioma-derived cell lines: Cellular proliferation, cytotoxicity, morphological and radioreceptor studies. Int J Cancer 41: 573–582PubMedCrossRefGoogle Scholar
  8. 8.
    Sporn MB, Todaro GJ (1980) Autocrine secretion and malignant transformation of cells. New Engl J Med 303: 878–880PubMedCrossRefGoogle Scholar
  9. 9.
    Rutka J, Rosenblum ML, Stern R, Ralston HJ III, Dougherty D, Biblin J, De Armond S (1989) Isolatiion and purification of growth factor with TGF-like activity from human malignant gliomas. J Neurosurg 71: 875–883PubMedCrossRefGoogle Scholar
  10. 10.
    Sara V, Prisell P, Sjogren B, Persson L, Boethhius J, Enberg G (1986) 32: 229–234Google Scholar
  11. 11.
    Helseth E, Unsgaar G, Dalen A, Vik R (1988) The effect of type beta transformaing growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma cell line. J Neurooncol 6: 267–276Google Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Jun Yoshida
  • Toshihiko Wakabayashi
  • Masaaki Mizuno
  • Hirofumi Oyama
  • Kyoko Nehashi
  • Kenichiro Sugita
    • 1
  1. 1.Department of NeurosurgeryNagoya University School of MedicineNagoya, 466Japan

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