Interleukin 6 is secreted by breast fibroblasts and stimulates 17β-oestradiol oxidoreductase activity of MCF-7 cells: Possible paracrine regulation of breast 17β-oestradiol levels

✍ Scribed by Eric F. Adams; B. Rafferty; M. C. White

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 472 KB
• Volume: 49
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910490122

✦ Synopsis

Abstract

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 17β‐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.