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Breast adenocarcinoma cell adhesion to the vascular subendothelium in whole blood and under flow conditions: Effects of α v β 3 and α IIb β 3 antagonists

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Abstract

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 αvβ3 and platelet αIIbβ3integrins 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 αIIbβ3 (lamifiban) or tumour cell αvβ3 (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 αIIbβ3 at higher shear rate. However, a combination of SB-273005 and lamifiban, or c7E3 Fab (a potent inhibitor of both αIIbβ3 and αvβ3) 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.

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Gomes, N., Vassy, J., Lebos, C. et al. Breast adenocarcinoma cell adhesion to the vascular subendothelium in whole blood and under flow conditions: Effects of α v β 3 and α IIb β 3 antagonists. Clin Exp Metastasis 21, 553–561 (2004). https://doi.org/10.1007/s10585-004-3756-4

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