E-selectin-mediated dynamic interactions of breast- 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 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.
Tözeren
A
A
Biomedical Engineering Program, Catholic University of America, Washington DC 20064.
Kleinman
H K
HK
Grant
D S
DS
Morales
D
D
Mercurio
A M
AM
Byers
S W
SW
D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism; D009362:Neoplasm Metastasis; D012212:Rheology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016023:Integrins; D014409:Tumor Necrosis Factor-alpha