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The Effects of Five Hematopoietic Growth Factors on Human Small Cell Lung Carcinoma Cell Lines: Interleukin 3 Enhances the Proliferation in One of the Eleven Cell Lines¹

Departments of Hematology [E. V., L. W., M. E.] and Medical Oncology [B. B., C. M., E. G. E. de V.], University Hospital Groningen, Oostersingel 59, 9713 E2 Groningen, The Netherlands

Eleven small cell lung carcinoma cell lines of human origin were exposed to different colony stimulating factors (CSFs) to study whether CSFs could enhance the spontaneous cell proliferation and modify the action of cytotoxic drugs. In ten cell lines no suppressive or stimulative effect was observed when measured in a [³H]thymidine assay and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. However, one cell line (GLC-20) could be stimulated by interleukin 3 (IL-3) when measured with a proliferative as well as a clonogenic assay. This enhancing effect was cell concentration dependent in the [³H]thymidine assay. Additional CSFs such as granulocyte-macrophage-CSF, granulocyte-CSF, IL-4, IL-6, insulin, or bombesin could not further augment the IL-3 supported proliferation. In addition, IL-3 binding studies demonstrated the presence of IL-3 receptors on the GLC-20 cells. Two types of receptors were demonstrated by Scatchard analysis: high affinity receptors (59 ± 4 sites/cell) with a dissociation constant (K_d) of 31 ± 9 pmol/liter; and low affinity receptors (1915 ± 91 sites/cell) with a K_d of 2.0 ± 0.8 nmol/liter. Finally, it was shown that the toxic effects of adriamycin and cisplatin on the proliferation of the GLC-20 cell line could partially be abrogated in the presence of IL-3. These data indicate that in some cases CSFs can modulate the proliferation of small cell lung carcinoma cell lines and interfere with the effects of chemotherapeutic drugs.

¹ This study was supported by the Netherlands Cancer Foundation, Grant GUKC 86-01. E. V. is a fellow of the Royal Netherlands Academy of Arts and Sciences.

² To whom requests for reprints should be addressed.

Received 2/ 8/90. Accepted 10/12/90.