Shear stress modulates the interaction of platelet-secreted matrix proteins with tumor cells through the integrin alphavbeta3

American Journal of Physiology. Cell Physiology
Karen LawlerDermot Kenny

Abstract

Interaction of tumor cells with the vascular wall is required for metastasis from the bloodstream. The precise interaction among 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. Tumor cells were perfused over LPS-treated human umbilical vein endothelial cells (HUVECs) at incremental venous shear rates from 50 to 800 s(-1). At a venous shear rate of 400 s(-1), 3% of adherent tumor cells formed pseudopodia under shear, a process we termed shear-induced activation. Because platelets promote tumor dissemination, we then investigated the effect of pretreating tumor cells with platelet releasate collected from activated platelet concentrate. We found that in the presence of platelet releasate, the number of tumor cells adhering to HUVECs increased and tumor "activation" occurred at a significantly lower shear rate of 50 s(-1). This was inhibited with acetylsalicylic acid. 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). T...Continue Reading

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Citations

Nov 11, 2008·European Journal of Applied Physiology·Yu-Wen ChenJong-Shyan Wang
Jan 31, 2013·Biomacromolecules·Christa L Modery-PawlowskiAnirban Sen Gupta
Jun 20, 2014·Clinical & Experimental Metastasis·Karl EganDermot Kenny
Aug 19, 2008·Current Oncology Reports·Jessie Villanueva, Meenhard Herlyn
Apr 28, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Eimear DunneDermot Kenny
Apr 28, 2006·American Journal of Physiology. Cell Physiology·Karen LawlerDermot Kenny
Oct 23, 2010·Expert Review of Molecular Diagnostics·Lourdes Basabe-DesmontsDermot Kenny
Jul 2, 2011·Fundamental & Clinical Pharmacology·Peter HendricksVictor Sanjit Nirmalanandhan
Jul 14, 2019·Journal of Thrombosis and Haemostasis : JTH·Robert H LeeAnirban Sen Gupta
Aug 14, 2009·Journal of Biomolecular Screening·Victor Sanjit Nirmalanandhan, G Sitta Sittampalam
May 20, 2009·Blood Reviews·Price Blair, Robert Flaumenhaft

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