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 lines.
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 (Kd) of 31 +/- 9 pmol/liter; and low affinity receptors (1915 +/- 91 sites/cell) with a Kd 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.
Department of Hematology, University Hospital Groningen, The Netherlands.
E
E
Vellenga
B
B
Biesma
C
C
Meyer
L
L
Wagteveld
M
M
Esselink
E G
EG
de Vries
D001839:Bombesin / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007377:Interleukin-3 / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D014407:Tumor Cells, Cultured
D007328:Insulin; D007377:Interleukin-3; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001839:Bombesin; D002945:Cisplatin