Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions

Accumulating evidence suggests that successful metastatic spread may depend on the ability of tumor cells to undergo extensive interactions with plate lets. However, the mechanisms mediating tumor cell adhesion to platelets un der conditions of flow remain largely unknown. Therefore, this study was de signed to analyze the ability of 3 human colon carcinoma cell lines (LS174T , COLO205, and HCT-8) to bind to surface-anchored platelets under flow and to identify the receptors involved in these processes. Immobilized platelet s support LS174T cell adhesion at wall shear stresses up to 1.4 dyn/cm(2). Our data suggest that platelets primarily recruit LS174T cells through a P- step, sequential process of adhesive interactions that shares common featur es but is distinct from that elaborated for neutrophils. Platelet P-selecti n mediates LS174T cell tethering and rolling in a PSGL-1- and CD24-independ ent manner, Moreover, platelet alpha(llb)beta(3)-integrins appear to be cap able of directly capturing LS174T cells from the fluid stream, and also con vert instantaneously transient tethers initiated by P-selectin into stable adhesion, This step is at least partially mediated by von Willebrand factor , but not fibrinogen or fibronectin, that bridges platelet alpha(llb)beta(3 ) With a yet unidentified receptor on the LS174T cell surface via an RGD-de pendent mechanism. The sequential engagement of platelet P-selectin and alp ha(llb)beta(3) is also requisite for the optimal adhesion of COLO205, Furth ermore, HCT-8 cells, which fail to interact with P-selectin, tether minimal ly to surface-anchored platelets under flow, despite their extensive adhesi ve interactions under static conditions. This cascade of events depicts an efficacious process for colon carcinoma arrest at sites of vascular injury, (C) 2000 by The American Society of Hematology.