Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 287, Issue 5, Pages C1320-C1327Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00159.2004
Keywords
platelet releasate; vitronectin; fibronectin
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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). The integrin alpha(v)beta(3) has been shown to mediate cell adhesion primarily through vitronectin and fibronectin proteins. Inhibition of alpha(v)beta(3), followed by the addition of platelet releasate to the tumor cells, resulted in significantly less adhesion at higher venous shear rates of 600 and 800 s(-1). Collectively, our data suggest that alpha(v)beta(3) promotes the metastatic phenotype of tumor cells through interactions with the secreted platelet proteins vitronectin and fibronectin under venous shear conditions.
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