Dexamethasone increases the expression of membrane macrophage colony stimulating factor from retrovirally transduced tumor cells expressing macrophage colony stimulating factor

Many different tumor cell types (breast, ovarian, glioma, liver and colon) were retrovirally transduced with the human macrophage colony stimulating f actor (M-CSF) gene (either the membrane associated form [mM-CSF] or the sec reted form [sM-CSF]). These cells were tested for their ability to display increased amounts of mM-CSF in response to dexamethasone. M-CSF-transfected tumor cells expressed additional mM-CSF in response to 18-72 h incubations with 3-15 mug/ml dexamethasone, while non-transfected parental cells were unaffected by this treatment, increased mM-CSF protein expression on the M- CSF transduced cells was observed by flow cytometry and Western blotting us ing M-CSF specific antibodies. Northern blot analysis revealed an increase in the mM-CSF specific transcripts within the dexamethasone-treated mM-CSF transduced cells, but this was not seen within the non-transfected tumor ce lls that were treated with dexamethasone. ICAM-1 expression was unaffected by dexamethasone treatment, indicating that this response is mM-CSF specifi c. All trans-retinal and 1,25-dihydroxy vitamin D3 compounds that have been reported to induce M-CSF expression failed to increase mM-CSF. When dexame thasone-treated mM-CSF transfected clones were used as target cells for mac rophage mediated cytotoxicity assays, an increased killing with the dexamet hasone-treated cells was seen. The macrophage-mediated cytotoxicity of thes e mM-CSF expressing tumor cells was blocked with excess recombinant M-CSF b y saturating M-CSF receptors on the macrophage that is required for this fo rm of tumor cell killing. This work suggests the possibility that dexametha sone may prove useful for vaccination purposes using mM-CSF retrovirally tr ansfected tumor cells. Published by Elsevier Science B.V.