RU 58668: further in vitro and in vivo pharmacological data related to its antitumoral activity.

Previous studies with the pure antiestrogen RU 58668 showed that this compound proved to be highly antiproliferative in vitro, and to be the only antiestrogenic compound so far known to induce long-term regression of MCF-7 tumours implanted into nude mice. In order to obtain more insight into the therapeutic potential of this molecule, we performed a new set of experiments in vitro and in vivo in comparison with tamoxifen and/or ICI 182,780. In vitro, 1 nM RU 58668 induced an accumulation of MCF-7 cells in G0/G1 phases of the cell cycle within 48 h and, in contrast to trans-4-hydroxy-tamoxifen, blocked the invasiveness of ras-transfected MCF-7 cells into the chick embryo heart during the three weeks of co-culture.

Alteration of prostaglandin E receptors in advanced breast tumour cell lines.

We studied the direct effects of PGE2, often produced at high levels by mammary tumours, on three human breast cancer cell lines diversely advanced in malignancy regarding differentiation and tumorigenicity in nude mice. We evaluated PGE2 effect on cell growth, PGE2 receptor level and functionality. Our results show that PGE2 induces cAMP accumulation and inhibits the growth of the most differentiated breast cancer cells.

Evidence for separate mechanisms of antiproliferative action of indomethacin and prostaglandin on MCF-7 breast cancer cells.

Indomethacin is reported to decrease the growth of many tumour cell lines. It is also known to be an anti-inflammatory agent acting by the inhibition of prostaglandin (PG) synthesis. To evaluate a clinical application as antitumoral agent, we have studied whether antiproliferative effect of indomethacin in breast cancer is related to its action on the prostaglandin production.

Fibroblast-mediated differentiation in human breast carcinoma cells (MCF-7) grown as nodules in vitro.

The growth of cells in 3-dimensional form as nodules in vitro facilitates studies of in vivo cellular interactions. Taking advantage of this technique, human breast carcinoma cells (MCF-7) were co-cultured with stromal fibroblasts isolated from either normal or tumorous breast tissue to study the influence of such fibroblasts on tumor-cell growth and differentiation. Ten days after co-culture of carcinoma cells with fibroblasts from normal tissue at a 1:10 ratio, the size of nodules began to increase and stabilize by day 30 while the fibroblast number decreased and finally disappeared.

Myofibroblast and concurrent ED-B fibronectin phenotype in human stromal cells cultured from non-malignant and malignant breast tissue.

Primary cultures of stromal cells from non-malignant and malignant breast tissues contained myofibroblasts based on immunoreactivity to alpha-smooth muscle (alpha-sm) actin. The proportions of these cells were variable among cultures from non-malignant origin while consistently high in cultures from carcinomas. High expression of ED-B fibronectin and of type V collagen was observed in myofibroblast-containing cultures.