INHIBITION OF ENDOTHELIAL ADHESION AND INVASION BY BREAST-CARCINOMA CELLS MAY CONTRIBUTE TOWARDS THE ANTIMETASTATIC EFFECTS OF TAMOXIFEN

The anti-metastatic actions of tamoxifen on the oestrogen receptor-(ER -) positive cell line, MCF-7 and Hs578T, which is ER-negative, were in vestigated by measuring changes in the tumour cell adherence to endoth elium and invasion of Matrigel, The endothelial hybridoma EA.hy926 was grown to confluence on the bases of 96-well plates, Either tamoxifen, the pure ER antagonist ICI 182,780 or the control, phosphate-buffered saline (PBS), was added to each well in varying concentrations, Adhes ion of tumour cells to the endothelium was then measured using an isot opic adhesion assay, Invasion was determined by measuring the number o f cells passing across a Matrigel-coated filter with 8 mu m diameter p ores, After 24-h incubation, the number of cells which had invaded was determined by an XTT colorimetric assay, Tamoxifen and ICI 182,780 in hibited both adhesion to the model endothelium and Matrigel invasion o f the ER-positive cell line at therapeutic concentrations (P<0.005), N either compound, however, had an effect on the ER-negative cell line. This action of the ER antagonists may play a role in prolonging the di sease-free survival seen in women with breast cancer who are treated w ith adjuvant tamoxifen.