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 platelets. However, the mechanisms mediating tumor cell adhesion to platelets under conditions of flow remain largely unknown. Therefore, this study was designed 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 platelets 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 2-step, sequential process of adhesive interactions that shares common features but is distinct from that elaborated for neutrophils. Platelet P-selectin mediates LS174T cell tethering and rolling in a PSGL-1- and CD24-independent manner. Moreover, platelet alpha(IIb)beta(3)-integrins appear to be capable of directly capturing LS174T cells from the fluid stream, and also convert 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(IIb)beta(3) with a yet unidentified receptor on the LS174T cell surface via an RGD-dependent mechanism. The sequential engagement of platelet P-selectin and alpha(IIb)beta(3) is also requisite for the optimal adhesion of COLO205. Furthermore, HCT-8 cells, which fail to interact with P-selectin, tether minimally to surface-anchored platelets under flow, despite their extensive adhesive interactions under static conditions. This cascade of events depicts an efficacious process for colon carcinoma arrest at sites of vascular injury. (Blood. 2000;96:1789-1797)
McCarty
O J
OJ
Department of Chemical Engineering, Department of Medicine, Johns Hopkins University, Baltimore, MD 21218-2694, USA.
Mousa
S A
SA
Bray
P F
PF
Konstantopoulos
K
K
D001696:Biomechanical Phenomena; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D003110:Colonic Neoplasms; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011485:Protein Binding; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000080506:Sialyl Lewis X Antigen; D014841:von Willebrand Factor