Cell to cell interactions and normal mammary gland function.

The nonepithelial components of the mammary gland are reviewed and their potential for regulatory cell-cell interactions with the epithelial cells are discussed. Studies undertaken to examine the regulatory potential of mammary stromal fibroblasts using an in vitro cell culture system are presented. The influence was examined of epithelial-fibroblast interactions on estrogenic regulation of progesterone receptor concentration in epithelial cells and on epithelial and fibroblast DNA synthesis. Mammary fibroblasts affect estrogen responsiveness in epithelial cells by two different mechanisms. In the case of progesterone receptor regulation, fibroblasts promote estrogen-dependent increases in the receptor via a substratum effect possibly by the production of collagen type I. By contrast, the fibroblast effect promoting estrogen-dependent cell proliferation requires fibroblasts to be metabolically active and in close contact with the epithelium. Additionally, under coculture conditions, estrogen-dependent stimulation of fibroblast DNA synthesis is also observed, indicating a bidirectional, interactive phenomenon between the two types of cells. It is possible that the modulations in epithelial responsiveness to estrogen that are associated with the presence of mammary fibroblasts in vitro reflect regulatory mechanisms that operate in vivo.