Role of metastatic potential in the adhesion of human breast cancer cells to endothelial monolayers

To gain further insight into the process of metastasis, adhesion to endothelial monolayers was compared for a nonmetastatic and a highly metastatic human breast cancer cell line. The parallel plate flow chamber was employed to quantify adhesion using an attachment assay. This assay was carried out at several physiological shear stresses both with and without endothelial TNF-α stimulation. At a venular shear stress of 1 dyne cm^-2, the nonmetastatic cell line was more adhesive to stimulated endothelial monolayers, while no differences could be noted for resting monolayers. At a lower shear stress of 0.25 dynes cm^-2, the highly metastatic cell line was more adhesive to stimulated endothelial monolayers, while the nonmetastatic cell line was more adhesive to resting monolayers. Thus, metastatic potential correlated with attachment only at low shear stresses and following endothelial stimulation. These results emphasize the importance of studying cancer cell adhesion under multiple physiological flow conditions. Furthermore, these results indicate that adhesion of these two cell lines may be controlled by two different mechanisms. Antibody blocking experiments of adhesion molecules on the endothelial cells confirmed that adhesion of the nonmetastatic cell line was mediated by E-selectin expressed on the endothelial cells and adhesion of the highly metastatic cell line was mediated by both E-selectin and VCAM-1 expressed on the endothelial cells.