title: Dexamethasone increases the expression of membrane macrophage colony stimulating factor from retrovirally transduced tumor cells expressing macrophage colony stimulating factor.
abstract: Many different tumor cell types (breast, ovarian, glioma, liver and colon) were retrovirally transduced with the human macrophage colony stimulating factor (M-CSF) gene (either the membrane associated form [mM-CSF] or the secreted 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 microg/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 using 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 cells that were treated with dexamethasone. ICAM-1 expression was unaffected by dexamethasone treatment, indicating that this response is mM-CSF specific. 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 dexamethasone-treated mM-CSF transfected clones were used as target cells for macrophage-mediated cytotoxicity assays, an increased killing with the dexamethasone-treated cells was seen. The macrophage-mediated cytotoxicity of these mM-CSF expressing tumor cells was blocked with excess recombinant M-CSF by saturating M-CSF receptors on the macrophage that is required for this form of tumor cell killing. This work suggests the possibility that dexamethasone may prove useful for vaccination purposes using mM-CSF retrovirally transfected tumor cells.
authors.affiliation: Diagnostic and Molecular Medicine Health Care Group, Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Dan
authors.forename: H
authors.initials: H
authors.lastname: Trinh
authors.forename: C C
authors.initials: CC
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Lloyd
authors.forename: H T
authors.initials: HT
authors.lastname: Wepsic
authors.forename: E W
authors.initials: EW
authors.lastname: Jeffes
authors.forename: M R
authors.initials: MR
authors.lastname: Jadus
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D003907:Dexamethasone / Q000494:pharmacology*; D015316:Genetic Therapy; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D008264:Macrophages / Q000502:physiology; D009369:Neoplasms / Q000628:therapy*; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor