Differential regulation of normal and tumoral breast epithelial cell growth by fibroblasts and 1,25-dihydroxyvitamin D-3

Mesenchymal-epithelial interactions are of paramount importance during norm al and tumoral breast developments. We have investigated the paracrine grow th regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast c ancer MCF-7 cells or normal epithelial cells in primary culture were cocult ured with fibroblasts in a Transwell system allowing diffusible factor exch anges. Alternatively, conditioned medium produced by fibroblast cultures wa s added to epithelial cell cultures. Fibroblasts were shown to stimulate th e proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D-rela ted compounds that have been proposed as anti-tumoral drugs were studied fo r their ability to affect normal and tumoral mammary epithelial cell prolif eration and to interfere with the growth-regulatory activity of fibroblasts . Whereas vitamin D compounds inhibited MCF-7 cell growth, they led to a ma rked stimulation of the proliferation of normal mammary epithelial cells. M oreover, it was shown that the vitamin D analog EB 1089 can block the mitog enic effect of fibroblast-conditioned medium on tumoral but not normal brea st epithelial cells. The differential effects of vitamin D compounds on cel l proliferation provide further data in favor of the different behaviours o f normal and tumoral mammary epithelial cells. The potential therapeutic us e of vitamin D derivatives in the treatment of breast cancer is supported b y these results but their growth-stimulatory properties on normal epithelia l cells cannot be overlooked.