Human stem cell factor (c-kit ligand) induces an autocrine loop of growth in a GM-CSF-dependent megakaryocytic leukemia cell line.
The M07e megakaryoblastic leukemia cell line is strictly dependent on either interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for continuous growth. This study shows that recombinant human stem-cell factor (rhSCF) can completely replace these lymphokines in supporting the continued propagation of M07e cells mostly by eliciting GM-CSF secretion in this target. In fact, in short-term proliferation assays the stimulatory activity of SCF is blocked about 75% by a GM-CSF-specific serum. In addition, we could detect GM-CSF expression by SCF-stimulated M07e cells, both at the protein and mRNA levels. In contrast, SCF does not induce transcripts for any other cytokine to which M07e cells are responsive, including IL-2, IL-3, IL-4, and IL-6. Overall, these data show that the ability of SCF to support the growth of this megakaryocytic cell line is mediated mostly by the induction of an autocrine loop of activation involving GM-CSF production. The finding that SCF can stimulate GM-CSF secretion also in an IL-2-dependent T-lymphoblastic leukemia cell line indicates that SCF can act on cells of both myeloid and lymphoid lineages, and that the ability to induce cytokines in target cells represents an important aspect of its mechanism of action.
Kiss
C
C
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Cesano
A
A
Zsebö
K M
KM
Clark
S C
SC
Santoli
D
D
D002455:Cell Division / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism / Q000473:pathology*; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor