Inhibition of endothelial adhesion and invasion by breast carcinoma cells may contribute towards the anti-metastatic 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 investigated by measuring changes in the tumour cell adherence to endothelium 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. Adhesion of tumour cells to the endothelium was then measured using an isotopic adhesion assay. Invasion was determined by measuring the number of cells passing across a Matrigel-coated filter with 8 microm diameter pores. After 24-h incubation, the number of cells which had invaded was determined by an XTT colorimetric assay. Tamoxifen and ICI 182,780 inhibited both adhesion to the model endothelium and Matrigel invasion of the ER-positive cell line at therapeutic concentrations (P<0.005). Neither compound, however, had an effect on the ER-negative cell line. This action of the ER antagonists may play a role in prolonging the disease-free survival seen in women with breast cancer who are treated with adjuvant tamoxifen.
Bliss
R D
RD
Department of Surgery Medical School, Newcastle upon Tyne, UK.
Kirby
J A
JA
Browell
D A
DA
Lennard
T W
TW
D000970:Antineoplastic Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003094:Collagen; D018572:Disease-Free Survival; D004338:Drug Combinations; D004727:Endothelium / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005109:Extracellular Matrix; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007797:Laminin; D011509:Proteoglycans; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D004338:Drug Combinations; D004965:Estrogen Antagonists; D007797:Laminin; D011509:Proteoglycans; D013629:Tamoxifen; C059485:matrigel; D000077267:Fulvestrant; D004958:Estradiol; D003094:Collagen