Masaaki Mizuno

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

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.