Influence of Antiestrogens on NIH-3T3-Fibroblast-Induced Motility of Breast Cancer Cells

Abstract

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.

Distinctive Features of Advancing Breast Cancer Cells and Interactions with Surrounding Stroma Observed Under the Scanning Electron Microscope

“…In their study, they showed that conditioned media from NIH 3T3 fibroblasts (3T3-CM) used as a chemoattractant in matrigel invasion chambers increases the invasiveness of breast cancer cells. Additionally, they found that MCF-7 breast cancer cells treated with 3T3-CM exhibit an increased rate of membrane ruffling of the plasma membrane and concluded that 3T3-CM increases the invasiveness of breast cancer in direct correlation with increased membrane ruffling (Rajah et al, 2001). Our SEM images reveal that the presence of membrane ruffles on the surface of breast cancer cells gives them a rougher appearance than normal breast cells.…”

“…Cytoskeleton rearrangement leads to disorganisation of the membrane of cancer cells. This is a result of changes to internal biopolymeric protein, an important component of the cell cytoskeleton, which subsequently alter the surface of cancer cells (Brinkley et al, 1980;Rajah et al, 2001;Kaul-Ghanekar et al, 2009).…”

Effect of Rapamycin on Hepatocyte Function and Proliferation Induced by Growth Factors

“…Mitogens stimulate cellular proliferation [11][12][13] , and in general, differentiated cellular functions are thought to be suppressed during cell proliferation [14,15] . However, recent studies showed that mitogens can also stimulate cellular functions such as protein production [16,17] .…”

Effect of Antiestrogens on EGF-Mediated Movement of Human Breast Cancer Cells

“…In this study, cell motility was quantified using TLVM as previously described [10] . Digital video-images captured at various time intervals over a 3-hour recording period were analyzed using the NIH Image (1.59) program.…”