Interleukin 6 is secreted by breast fibroblasts and stimulates 17 beta-oestradiol oxidoreductase activity of MCF-7 cells: possible paracrine regulation of breast 17 beta-oestradiol levels.
Previous studies have demonstrated that cultured human breast fibroblasts secrete a high-molecular-weight polypeptide which stimulates the ability of human breast-cancer MCF-7 cells to convert oestrone (E1) to the biologically more active 17 beta-oestradiol (E2). This effect is mediated by an increase in reductive E2 oxidoreductase (EOR) activity. We have identified the fibroblast-derived stimulatory factor as interleukin 6 (IL6) or an immunologically related peptide. Human breast fibroblasts in culture secreted up to 10 ng IL6/ml medium during 24 hr of incubation. The effects of IL6 and breast fibroblast conditioned medium (CM) on reductive EOR activity of MCF-7 cells were similar; both CM and IL6 potently stimulated enzyme activity in a dose-dependent manner, and both exerted synergistic stimulatory effects in combination with E2. A polyclonal neutralizing antibody to IL6 completely abolished the reductive EOR-stimulating activity of CM. These results indicate that breast stromal fibroblasts may have a paracrine role in regulation of breast-cancer-tissue levels of E2, and that this effect is mediated by IL6 or a closely related peptide.
Adams
E F
EF
Department of Medicine, Royal Liverpool Hospital, UK.
Rafferty
B
B
White
M C
MC
D001940:Breast / Q000166:cytology / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004960:Estradiol Dehydrogenases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D011994:Recombinant Proteins; D004960:Estradiol Dehydrogenases