EFFECT OF STROMAL AND EPITHELIAL-CELLS DERIVED FROM NORMAL AND TUMOROUS BREAST-TISSUE ON THE PROLIFERATION OF HUMAN BREAST-CANCER CELL-LINES IN COCULTURE

Stromal and epithelial components surrounding neoplastic cells are bel ieved to be important in tumor regulation. We have studied the effects of stromal and epithelial cells on the proliferation of a variety of breast-cancer epithelial cell lines. Co-culture experiments were perfo rmed in which the 2 cell types were separated by a microporous membran e. Under these conditions, fibroblasts from normal breast tissues inhi b ited the proliferation of MCF-7 cells, but not that of immortalized normal S2T2 cells. In contrast, fibroblasts from cancerous breast tiss ues did not influence the proliferation of the 2 cell lines tested. Co nditioned media (CM) of breast fibroblasts derived from normal tissues were not able to affect MCF-7 cell growth, suggesting complex paracri ne interactions between both cell types. Normal breast epithelial cell s (NBEC) have also been tested for their ability to regulate the proli feration of breast-cancer epithelial cell lines. Co-culture experiment s demonstrated that NBEC inhibited a variety of breast-cancer cell lin es. CM from NBEC induced similar results and the inhibitory effect app eared to be specific for epithelial cells from tumorous breast. Moreov er, CM from NBEC and normal fibroblasts were shown to contain more TGF (beta 1) and amphiregulin than those of MCF-7 cells. We conclude that both the tissue origin and the target tumor cell's phenotype will dete rmine the extent of proliferative response. More important, the tumor- cell growth inhibition induced by fibroblasts and epithelial cells of normal breast tissue may constitute a tumor-growth-regulatory mechanis m. (C) 1997 Wiley-Liss, Inc.