Chemokine-Independent VLA-4/VCAM-1–Mediated Rolling and Arrest of B16 Melanoma Cells Under Shear

Background: Integrins and other cell adhesion molecules play a critical role in 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. Methods: B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 was 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. Results: 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. Conclusions: 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.