Interaction of tumour cells with the vascular wall is required for metastasis from the blood stream. The precise interaction between metastatic cells, circulating platelets, the vessel wall and physiological flow conditions remains to be determined. In this study we investigated the interaction of shear on metastatic cell lines adherent to lipopolysaccharide (LPS) treated endothelium. Tumour cells were perfused over LPS treated human umbilical vein endothelial cells (HUVECs) at incremental venous shear rates from 50s^-1 to 800 s^-1. At a venous shear rate of 400 s^-1, 3% of adherent tumour cells formed pseudopodia under shear, a process we termed shear-induced activation. As platelets promote tumour dissemination, we then investigated the effect of pre-treating tumour cells with platelet releasate collected from activated platelet concentrate. We found that in the presence of platelet releasate, the number of tumour cells adhering to HUVECs increased and tumour activation occurred at a significantly lower shear rate of 50 s^-1. This was inhibited with aspirin. Depletion of fibronectin or vitronectin from the platelet releasate resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s^-1. The integrin aVb3 has been shown to mediate cell adhesion primarily through vitronectin and fibronectin proteins. Inhibition of aVb3, followed by addition of platelet releasate to our tumour cells resulted in significantly less adhesion at higher venous shear rates of 600 and 800s^-1. Collectively, our data suggests that aVb3 promotes the metastatic phenotype of tumour cells through interactions with secreted platelet proteins vitronectin and fibronectin under venous shear conditions.