Antiproliferative and differentiative effect of granulocyte-macrophage colony-stimulating factor on a variant human...

A variant clone was adopted during passages of a small cell lung cancer cell line, GKT3-1.3. The variant clone exhibited distinct characteristics with alterations in morphology, positive staining with nonspecific esterase stain, and an increase in surface specific markers OKM5, HLA-DR, Mo1, and My7, usually found on monocytes or their precursors. However, it exerted a very rapid proliferation just like immature cells. This new clone, GKT3-1.3V, was shown to have specific binding capacity to granulocyte-macrophage colony-stimulating factor (GM-CSF), with a number of binding sites comparable to that of myelomonocytes or monocytic cell lines. Thus its proliferation was inhibited by GM-CSF in clonogenic assay and suspension culture. Increase in the percentage of cells with surface marker Mo1 by the addition of GM-CSF suggested its differentiative effect. Cell cycle analysis showed that the antiproliferative effect of GM-CSF was due to a block in G0 or G1. The antiproliferative effect of GM-CSF was abolished by the addition of anti-GM-CSF antibody.