Selective interactions between mammary epithelial cells and fibroblasts in co-culture.

Paracrine interactions between breast-cancer cells (MCF7) and stromal fibroblasts were studied in relation to the presence of steroid hormones, using co-cultures in which the 2 populations were separated by a microporous membrane. Densities and DNA-synthesis rates of the co-existing populations were interrelated. Proliferation was, therefore, viewed as the cumulative result of several factors, some of which are non-specific, e.g., are density-dependent, and some are specifically related to the feeders' origin and/or to culture conditions. Specific effects were measured and evaluated by stepwise analysis of covariance. MCF7 stimulated proliferation of fibroblasts differentially. Malignant-tumour fibroblasts were stimulated more than non-pathological ones. The magnitude of these effects was dependent on the presence of steroids. A similar analytical method was used for evaluating differential stromal influences on 4 epithelial phenotypic characters commonly used as prognostic markers. The estrogen-receptor, progesterone-receptor, pS2 and cathepsine-D phenotypes of MCF7, as well as their interrelations, were dependent on the origin of the fibroblasts, i.e., embryonic or adult, normal or tumoral.