Influence of antiestrogens on the invasiveness and laminin attachment of breast cancer cells.
Metastatic spread of breast cancer is responsible for most of the morbidity and mortality associated with this disease. Thus, it is important to identify agents with antimetastatic activity. Because invasiveness and tumor cell attachment are fundamental steps in the metastatic cascade, the major objective of the present study was to evaluate the antimetastatic potential of three antiestrogens, each with different chemical structure and mechanism of action, on breast cancer cell invasiveness and laminin attachment. The antiestrogens examined were tamoxifen, a mixed antagonist/agonist; Analog II, a cyclopropyl antiestrogen with pure antagonist activity; and ICI-182,780, a steroidal antiestrogen with pure antagonist activity. Our results indicate that MDA-MB-231 human breast cancer cells are much more invasive and have a higher affinity for laminin than do MCF-7 human breast cancer cells. All three antiestrogens, at a concentration of 10(-6) M, produced a reduction in MDA-MB-231 cell invasiveness, which was comparable in magnitude to their inhibition of MDA-MB-231 attachment to laminin. Evaluation of MDA-MB-231 cell morphology using scanning electron microscopy revealed the involvement of cellular pseudopodia and microvilli in the process of invasion. The results of this study suggest that antiestrogen-induced inhibition of breast cancer cell invasiveness could be due in part to a decrease in the attachment of tumor cells to laminin in the basement membrane.
Rajah
T T
TT
Department of Pharmacology and Toxicology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Pento
J T
JT
D000230:Adenocarcinoma / Q000473:pathology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011509:Proteoglycans; D011554:Pseudopodia / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D004338:Drug Combinations; D020847:Estrogen Receptor Modulators; D007797:Laminin; D011509:Proteoglycans; D013629:Tamoxifen; C059485:matrigel; D000077267:Fulvestrant; D004958:Estradiol; C035174:tamoxifen analog II; D003094:Collagen