Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: Secretion of a polypeptide which stimulates reductive 17β-oestradiol dehydrogenase activity

Abstract

We have previously shown that a stroma‐associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17ß‐oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17ß‐oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor. In vitro cell culture techniques were used, in which human breast fibroblast‐conditioned medium was used to grow the human breast cancer cell line, MCF‐7, for 6 days, after which the reductive HSD activity of the monolayers was assessed. The fibroblastic reductive HSD stimulating factor was found to be a trypsinsensitive polypeptide. The polypeptide eluted from a Sephadex G‐75 column as a peak corresponding to a molecular weight of about 50 kDa. The polypeptide exerts its effects by altering the V_max of 2 of the cytosolic forms of HSD within MCF‐7 cells. This is achieved by a protein‐synthesis‐dependent but calmodulin‐independent mechanism. These results provide further evidence of a paracrine effect by stromal tissue within the human breast and have important implications with respect to the aetiology and treatment of breast cancer.