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Growth Inhibition of Human Lung Cancer Cell Lines by Interleukin 6 in Vitro: A Possible Role in Tumor Growth via an Autocrine Mechanism¹

Department of Medicine and Physical Therapy, Tokyo University School of Medicine [H. T., T. O., K. O., N. Y., S. H., K. H., K. I.], and Department of Bacteriology, Juntendo University School of Medicine [Ke. H.], Tokyo, Japan

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 ß 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 ß, and could not be neutralized by the addition of anti-transforming growth factor ß 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.

¹ This work was supported by Manabe Medical Foundation.

² To whom requests for reprints should be addressed, at Department of Medicine and Physical Therapy, Tokyo University School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Received 3/ 8/93. Accepted 7/ 7/93.

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