Influence of stroma-derived growth factors on the estradiol­ stimulated prolif era ti on of human breast cancer cells

Purpose of investigation: Estradiol is the main proliferating substance for human epithelial breast cells. There is evidence that proliferation is also stimulated by growth factors mainly synthesized by the surrounding stroma. In the present in vitro study we have compared the proliferating activity of three growth factors alone and in combination with estradiol in human breast cancer cells.

Method: As a cell model the well-recognized human breast cancer cell line MCF-7 was used. The growth factors tested were basic fibroblast growth factor (bFGF), epithelial growth factor (EGF) and insulin-growth factor-1 (IGF-I) at the concentrations 10(-10), 10(-9) and 10(-8) M alone and in equimolar combination with 10(-10) M estradiol. Cell proliferation was measured after seven days incubation by the ATP-assay.

Results: The growth factors alone significantly stimulated proliferation of MCF-7 cells in the tested concentration range. The increases were about 40% for EGF, between 40 and 60% for FGF and between 30 and 90% for IGF-I. The strongest proliferating factor was estradiol alone with values between 70 and 130%. For all three growth factors an additive effect was seen in combination with estradiol, which was greatest for IGF-I.

Conclusion: These data indicate that estradiol is the strongest proliferating factor for human breast cancer cells. Therefore the predictive value of cell models using estradiol as a proliferative agent seems to be highly reliable. However, stromal influence by growth factors should not be disregarded, since proliferation of pre-existing malignant cells may be accelerated by the concomitant presence of estrogens and growth factors.

Estradiol; Growth factors; Proliferation; Human breast cancer cells

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