ROLE OF TUMOR-DERIVED FIBROBLASTS IN THE GROWTH OF PRIMARY CULTURES OF HUMAN BREAST-CANCER CELLS - EFFECTS OF EPIDERMAL GROWTH-FACTOR AND THE SOMATOSTATIN ANALOG OCTREOTIDE

In the present study we have investigated the role of human breast-can cer-derived fibroblasts in the proliferation of primary cultures of ep ithelial cells derived from the same tumor. For this purpose, a co-cul ture system, using Transwell tissue-culture inserts with microporous m embranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients . The coculture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17 beta-estrad iol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF w ere additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promot ing compounds, are responsible for the growth-promoting effects of fib roblasts. In half of the human breast cancers investigated, tumor-deri ved fibroblasts stimulated tumor-derived epithelial cell proliferation . EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were add itive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblast s. In one culture the fibroblasts significantly inhibited epithelial t umor-cell proliferation. Conversely, the epithelial cells significantl y stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial ce ll proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide signif icantly inhibited the proliferation of fibroblasts co-cultured with ep ithelial cells. (C) 1995 Wiley-Liss, Inc.