Integrins and other cell adhesion molecules play a critical role in the migration and homing of leukocytes. This study investigates whether metastatic tumor cells can exploit leukocyte-like rolling and arrest mechanisms during early vascular steps of metastatic dissemination. B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 were analyzed under defined shear flow using a parallel-plate chamber. Function-blocking antibodies, divalent cation modulation, pertussis toxin, and low-temperature conditions were used as classical controls. B16-BL6 melanoma cells exhibited robust VLA-4-dependent rolling and arrest on activated endothelial monolayers and on immobilized VCAM-1 under physiological shear stresses (0.7–2 dyn/cm2), independent of chemokine-related Gαi signaling. These findings identify a chemokine-independent mechanism of VLA-4-mediated vascular capture by melanoma cells under shear flow, providing a potential mechanistic basis for early steps in metastatic dissemination.
Robert H. Eibl (Sun,) studied this question.