E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers
Department of Cancer Biology
Breast Neoplasms; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Colonic Neoplasms; E-Selectin; Endothelium, Vascular; Humans; Integrins; Neoplasm Metastasis; Rheology; Tumor Necrosis Factor-alpha
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 monolayers. MCF-10A breast, MCF-7 and T-47D breast-carcinoma and clone A, RKO, and HT-29 colon-carcinoma 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 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 rolled 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 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.
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Citation: Int J Cancer. 1995 Jan 27;60(3):426-31.
Tozeren, Aydin; Kleinman, Hynda K.; Grant, Derrick S.; Morales, David; Mercurio, Arthur M.; and Byers, Stephen W., "E-selectin-mediated dynamic interactions of breast- and colon-cancer cells with endothelial-cell monolayers" (1995). Cancer Biology Publications and Presentations. Paper 131.