Influence of antiestrogens on NIH-3T3-fibroblast-induced motility of breast cancer cells

The motile behavior of tumor cells is regulated in part by growth factors, cytokines, and other endogenous factors. In some instances, stromal tissue surrounding the tumor cells produces these growth factors which interact wi th tumor cells and thus may play an important role in tumor proliferation a nd progression. We and others have shown that conditioned media from NIH 3T 3 fibroblasts (3T3-CM) increases the invasiveness of breast cancer cells. T he present study characterized the influence of 3T3-CM on breast cancer cel l motility and examined the hypothesis that antiestrogens inhibit this 3T3- CM-induced effect. In this study we observed that 3T3-CM added to MCF-7 cel ls produced an immediate cell-scattering effect as determined by time-lapse videomicroscopy, scanning electron microscopy, and F-actin labeling. The r esults of this study indicate that keratinocyte growth factor in 3T3-CM is largely responsible for the 3T3-CM-induced scattering motility of MCF-7 cel ls. These results emphasize the importance of stromal-tumor cell (epithelia l-mesenchymal) interactions in the motility of breast cancer cells. Further , our results demonstrate that antiestrogens (tamoxifen, ICI-182,780 and An alog II) inhibit 3T3-CM-induced motility of MCF-7 breast cancer cells. Anti estrogen treatment reduced membrane movements and the motile morphology of MCF-7 cells induced by 3T3-CM. These results suggest that antiestrogens inh ibit breast cancer cell motility and that antiestrogen treatment may be use d to reduce the metastatic spread of breast cancer. Copyright (C) 2001 S. K arger AG, Basel.