Lu-ECAM-1-mediated adhesion of melanoma cells to endothelium under conditions of flow.
Lu-ECAM-1 is a lung-derived, venular endothelial cell adhesion molecule. It promotes the selective adhesion of lung-metastatic B16-F10 melanoma cells to endothelium under static conditions and mediates colonization of the lungs by the same tumor cells. To test whether Lu-ECAM-1 by itself is sufficient to cause vascular arrest of B16-F10 cells, we measured here under conditions of flow tumor cell adhesion to endothelia that express different amounts of Lu-ECAM-1 on their surfaces. At physiological shear stresses, adhesion of B16-F10 melanoma cells to endothelia correlates positively with the amount of Lu-ECAM-1 expression on the endothelial cell surface and inversely with the level of the applied shear stress. Tumor cell trajectories are biphasic; i.e., B16-F10 melanoma cells initially move along the endothelial surface with a velocity similar to the theoretical velocity, then arrest within a fraction of a second. Arrest is permanent for most B16-F10 melanoma cells at all shear stresses tested. Tumor cells never engaged in a rolling motion prior to arrest. Masking of the Lu-ECAM-1 ligand on the surface of B16-F10 melanoma cells with soluble Lu-ECAM-1 impedes arrest of tumor cells on the surface of the test endothelium. Purified Lu-ECAM-1 also mediates B16-F10 arrest, but arrest is mostly transient at shear stresses of 0.59 dynes/cm2 and higher, implying adhesion by single receptor/ligand bonds. Our data suggest that Lu-ECAM-1 plays a critical role in the recognition and initial arrest of murine melanoma cells in lung venules.
Goetz
D J
DJ
School of Chemical Engineering, Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
el-Sabban
M E
ME
Hammer
D A
DA
Pauli
B U
BU
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D008024:Ligands; C071433:Lu-ECAM-1 protein, Bos taurus