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 with tumor cells and thus may play an important role in tumor proliferation and progression. We and others have shown that conditioned media from NIH 3T3 fibroblasts (3T3-CM) increases the invasiveness of breast cancer cells. The present study characterized the influence of 3T3-CM on breast cancer cell 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 cells produced an immediate cell-scattering effect as determined by time-lapse videomicroscopy, scanning electron microscopy, and F-actin labeling. The results of this study indicate that keratinocyte growth factor in 3T3-CM is largely responsible for the 3T3-CM-induced scattering motility of MCF-7 cells. These results emphasize the importance of stromal-tumor cell (epithelial-mesenchymal) interactions in the motility of breast cancer cells. Further, our results demonstrate that antiestrogens (tamoxifen, ICI-182,780 and Analog II) inhibit 3T3-CM-induced motility of MCF-7 breast cancer cells. Antiestrogen treatment reduced membrane movements and the motile morphology of MCF-7 cells induced by 3T3-CM. These results suggest that antiestrogens inhibit breast cancer cell motility and that antiestrogen treatment may be used to reduce the metastatic spread of breast cancer.