Modulation of human breast cancer cell adhesion by estrogens and antiestrogens

In order to study the effect of estrogens and antiestrogens on the adhesive properties of human breast cancer cells, the attachment on endothelial cells (EC), on subendothelial extracellular matrix (ECM) and on ECM components (collagen I and IV, laminin, fibronectin) of estrogen-dependent (MCF-7, ZR75-1) and estrogen-independent (BT-20) breast cancer cell lines was investigated. The cells were grown under conditions of controlled exposure to estrogen [17 beta-estradiol (E2)] and/or antiestrogens [tamoxifen (Tam) or 4-hydroxytamoxifen (OH-Tam)]. Treatment by E2 enhanced the ability of ZR75-1 cells to adhere to the various substrates, which contrasts with the observed absence of effects with the BT-20 cells. Similarly, Tam or OH-Tam induced a reduction of the adhesion of ZR75-1 tumor cell, but not of BT-20 cells. This effect was reversed by competing concentrations of E2. The effects on MCF-7 cell adhesion were similar to those described for ZR75-1 cells, but could not be reproducibly observed. Adhesion assays carried out with ZR75-1 cells grown in the absence or presence of phenol red, a pH indicator which behaves as a weak estrogen, led to a similar pattern of cell attachment. Conditioned media harvested from E2- or Tam-treated ZR75-1 cells failed to induce any effect on adhesion of other ZR75-1 cells grown in E2-deprived medium, suggesting that secretory activities are not required for the control of cell adhesiveness. The results suggest that estrogens and antiestrogens can control the adhesive behavior of breast tumor cells through their hormone responsive structures possibly by regulating expression of cell adhesion proteins and/or their cell surface receptors.