Gomes Noëlia, Legrand Chantal, Fauvel-Lafève Françoise
INSERM, U 553: IFR 105, Institut d'Hématologie, Université Paris VII Denis Diderot, Paris, France.
Clin Exp Metastasis. 2005;22(3):215-23. doi: 10.1007/s10585-005-7359-5.
Endothelial cells in vivo are exposed to blood shear forces and flow perturbations induce their activation. Such modifications of hemodynamic can be observed in patients with cancer. We have submitted endothelial cells (HUVEC) to shear stress (13 dynes/cm(2)) and isolated their extracellular matrix (ECM) prior perfusion with breast adenocarcinoma cells (MDA-MB-231) in whole blood at a shear rate of 1500 s(-1). Exposure of HUVEC to 13 dynes/cm(2) (tau(13)) for 2 h enhanced the secretion of von Willebrand factor (vWF) and thrombospondin-1 (TSP-1) in the ECM. Moreover, MDA-MB-231 cell adhesion was enhanced to such treated-ECM. This over-adhesion was inhibited by pre-incubating the ECM with anti-vWF or anti-TSP-1 antibodies, or by blocking tumour cell alpha(v)beta(3) integrin. Although blood platelets were involved in tumour cell adhesion to ECM, blockade of platelet GPIb or alpha(IIb)beta(3) receptors did not specifically inhibit the enhanced tumour cell adhesion observed on tau(13). ECM. These findings indicate that shear stress can modulate the expression of adhesive proteins in ECM, which favours direct tumour cell adhesion via alpha(v)beta(3) and other receptors.
体内的内皮细胞会受到血流剪切力的作用，而血流扰动会促使其激活。这种血流动力学的改变在癌症患者中也能观察到。我们将内皮细胞（人脐静脉内皮细胞，HUVEC）置于剪切应力（13达因/平方厘米）下，在以1500秒⁻¹的剪切速率用全血灌注乳腺癌细胞（MDA-MB-231）之前，分离出其细胞外基质（ECM）。将HUVEC暴露于13达因/平方厘米（τ₁₃）2小时，可增强ECM中血管性血友病因子（vWF）和血小板反应蛋白-1（TSP-1）的分泌。此外，MDA-MB-231细胞对这种处理过的ECM的黏附增强。用抗vWF或抗TSP-1抗体预孵育ECM，或阻断肿瘤细胞的α(v)β(3)整合素，可抑制这种过度黏附。尽管血小板参与了肿瘤细胞与ECM的黏附，但阻断血小板糖蛋白Ib或α(IIb)β(3)受体并不能特异性抑制在τ₁₃处理的ECM上观察到的增强的肿瘤细胞黏附。这些发现表明，剪切应力可调节ECM中黏附蛋白的表达，这有利于肿瘤细胞通过α(v)β(3)及其他受体直接黏附。
