Tumour cell adhesion to vascular extracellular matrix (ECM), an important step of metastatic progression, is promoted by platelets. The aim of our study was to investigate, in whole blood under venous and arterial shear conditions, the respective role of tumour cell a v b 3 and platelet a IIb b 3 integrins in MDA-MB-231 breast adenocarcinoma cell adhesion to human umbilical vein endothelial cell ECM. For that purpose, blood containing MDA-MB-231 cells was incubated with non-peptide antagonists specific for platelet a IIb b 3 (lamifiban) or tumour cell a v b 3 (SB-273005). At 300 s )1 , each antagonist used alone did not modify tumour cell adhesion, whereas, at 1500 s )1 , tumour cell adhesion was decreased by 25% in presence of lamifiban indicating a role of platelet a IIb b 3 at higher shear rate. However, a combination of SB-273005 and lamifiban, or c7E3 Fab (a potent inhibitor of both a IIb b 3 and a v b 3 ) inhibited tumour cell adhesion by 40-45%, at either shear rate applied, indicating a cooperation between these two integrins in MDA-MB-231 cell adhesion to ECM, as well as the participation of other adhesive receptors on tumour cells and/or platelets. Thus, efficient anti-metastatic therapy should target multiple receptors on tumour cells and platelets. Abbreviations: BSA -bovine serum albumin; DMEM -dulbecco modified eagle medium; ECM -extracellular matrix; EDTA -ethylenediaminetetraacetic acid; FITC -fluorescein isothiocyanate; HEPES -N-[2-hydroxyethyl]piperazine-N¢-[2-ethanesulfonic acid]; HUVEC -human umbilical vein endothelial cells; IgG -immunoglobulin;