Takizawa H, Ohtoshi T, Ohta K, Yamashita N, Hirohata S, Hirai K, Hiramatsu K, Ito K
Department of Medicine and Physical Therapy, Tokyo University School of Medicine, Japan.
Cancer Res. 1993 Sep 15;53(18):4175-81.
It has been considered that growth of human lung cancer cells, like other malignant cells, is positively and negatively regulated by a variety of growth factors via autocrine as well as paracrine mechanisms. The autocrine mechanism is considered to be important in the autonomy of proliferation of cancer cells. Recently, the role of autocrine growth-inhibiting factors such as transforming growth factor beta attracts special attention for better understanding of growth regulation of malignant cells. Here, we have demonstrated that a multifunctional cytokine interleukin 6 (IL-6) had an inhibitory effect on the proliferation of human non-small cell lung cancer cell lines, as shown by the growth accelerating effect of the specific anti-IL-6 antibody as well as the effect of exogenously added IL-6. Moreover, IL-6 can be expressed and released by human lung cancer cells, and these cells had specific IL-6 receptors on their cell surfaces, suggesting an autocrine mechanism. The growth-inhibitory effect of IL-6 was additive to that of transforming growth factor beta, and could not be neutralized by the addition of anti-transforming growth factor beta antibody. These results suggested that IL-6 may function as another class of autocrine growth-inhibiting factor in the growth regulation of human lung cancer. Relatively lower IL-6 sensitivity of these cells than noncarcinogenic human bronchial epithelial cells also suggested that escape from growth regulation by inhibitory factors such as IL-6 could be involved in lung cancer oncogenesis.
人们认为，与其他恶性细胞一样，人类肺癌细胞的生长受到多种生长因子通过自分泌和旁分泌机制的正向和负向调节。自分泌机制被认为在癌细胞增殖的自主性中起重要作用。最近，诸如转化生长因子β等自分泌生长抑制因子的作用因对更好地理解恶性细胞的生长调节而受到特别关注。在此，我们已经证明，一种多功能细胞因子白细胞介素6（IL-6）对人类非小细胞肺癌细胞系的增殖具有抑制作用，这表现为特异性抗IL-6抗体的生长促进作用以及外源性添加IL-6的作用。此外，IL-6可由人类肺癌细胞表达和释放，并且这些细胞在其细胞表面具有特异性IL-6受体，提示存在自分泌机制。IL-6的生长抑制作用与转化生长因子β的作用相加，并且不能通过添加抗转化生长因子β抗体而被中和。这些结果表明，IL-6可能作为另一类自分泌生长抑制因子在人类肺癌的生长调节中发挥作用。这些细胞相对于非致癌性人类支气管上皮细胞对IL-6的敏感性较低，这也表明逃避诸如IL-6等抑制因子的生长调节可能参与肺癌的发生。
