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, if is important to ident ify agents with antimetastatic activity. Because invasiveness and tumor cel l attachment are fundamental steps in the metastatic cascade, the major obj ective of the present study was to evaluate the antimetastatic potential of three antiestrogens, each with different chemical structure ansi mechanism of action, on breast cancer cell invasiveness and laminin attachment. The antiestrogens examined were tamoxifen, a mixed antagonist/agonist; Analog I I, a cyclopropyl antiestrogen with pure antagonist activity and ICI-182,780 , a steroidal antiestrogen with pure antagonist activity. Our results indic ate that MDA-MB-231 human breast cancer cells are much more invasive and ha ve a higher affinity for laminin than do MCF-7 human breast cancer cells. A ll three antiestrogens, at a concentration of 10(-6) M, produced a reductio n in MDA-MB-231 cell invasiveness, which was comparable in magnitude to the ir inhibition of MDA-MB-231 attachment to laminin. Evaluation of MDA-MB-231 cell morphology using scanning electron microscopy revealed the involvemen t of cellular pseudopodia and microvilli in the process of invasion. The re sults of this study suggest that antiestrogen-induced inhibition of breast cancer cell invasiveness could he due in parr to a decrease in the attachme nt of tumor cells to laminin In the basement membrane.