Lu-ECAM-1-mediated adhesion of melanoma cells to endothelium under conditions of flow

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Abstract
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. © 1996 Wiley‐Liss, Inc.