The molecular mechanisms involved in the dynamic interaction of human breast carcinoma cells with the endothelial cell lining of lymphatic vessels and post-capillary blood venules are largely unknown. In the present study, laminar flow assays were used to investigate the ability of various normal breast cells and of breast-and colon-tumor cells to adhere to human umbilical cord endothelial cell monolayen. MCF-I OA breast, MCF-7 and T-47D breast-carcinoma and clone A. RKO, and HT-29 coloncarcinoma cells accumulated and rolled, in the presence of flow. on tumor necrosis factor (TNF)-stimulated but not on unstimulated endothelial cell monolayers. Non-tumor and tumor cells continued to form transient adhesions with TNF-stimulated endothelial cells even when the flow rate was increased to levels found in arteries. Incubation of TNF-stimulated endothelial cells with an E-selectin-specific monoclonal antibody (MAb) partially or completely inhibited dynamic interactions and diminished adhesion strength, whereas integrin PIand integrin %-specific MAbs had no effect. A set of highly invasive breast-carcinoma cells (MDA-23 I, BT-549, HS-578t) neither adhered to nor rolled on resting or TNF-stimulated endothelial cell monolayen. However, after 5 min of static incubation, a fraction of these cells attached strongly to resting and TNF-stimulated endothelial cells and this static adhesion could not be blocked by an E-selectin-specific monoclonal antibody. Our results suggest that E-selectin is a major homing receptor in the metastasis of some breast and colon cancers.