E-SELECTIN-MEDIATED DYNAMIC INTERACTIONS OF BREAST-CANCER AND COLON-CANCER CELLS WITH ENDOTHELIAL-CELL MONOLAYERS

The molecular mechanisms involved in the dynamic interaction of human breast carcinoma cells with the endothelial cell lining of lymphatic v essels and post-capillary blood venules are largely unknown. In the pr esent 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 monolayers. MCF-10A b reast, MCF-7 and T-47D breast-carcinoma and clone A, RKO, and HT-29 co lon-carcinoma cells accumulated and rolled, in the presence of now, on tumor necrosis factor (TNF)-stimulated but not on unstimulated endoth elial cell monolayers. Non-tumor and tumor cells continued to form tra nsient adhesions with TNF-stimulated endothelial cells even when the f low rate was increased to levels found in arteries. Incubation of TNF- stimulated endothelial cells with an E-selectin-specific monoclonal an tibody (MAb) partially or completely inhibited dynamic interactions an d diminished adhesion strength, whereas integrin beta(1)- and integrin alpha(6)-specific MAbs had no effect. A set of highly invasive breast -carcinoma cells (MDA-231, BT-549, HS-578t) neither adhered to nor rol led on resting or TNF-stimulated endothelial cell monolayers. However, after 5 min of static incubation, a fraction of these cells attached strongly to resting and TNF-stimulated endothelial cells and this stat ic adhesion could not be blocked by an E-selectin-specific monoclonal antibody. Our results suggest that E-selectin is a major homing recept or in the metastasis of some breast and colon cancers. (C) 1995 Wiley- Liss, Inc.