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Shear Stress Induced Release of Von Willebrand Factor and Thrombospondin-1 in Uvec Extracellular Matrix Enhances Breast Tumour Cell Adhesion

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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/cm2) 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/cm2 (τ13) 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 αvβ3 integrin. Although blood platelets were involved in tumour cell adhesion to ECM, blockade of platelet GPIb or αIIbβ3 receptors did not specifically inhibit the enhanced tumour cell adhesion observed on τ13. ECM. These findings indicate that shear stress can modulate the expression of adhesive proteins in ECM, which favours direct tumour cell adhesion via αvβ3 and other receptors.

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Abbreviations

BSA:

bovine serum albumin

DMEM:

Dulbecco modified eagle medium

ECM:

extracellular matrix

EDTA:

ethylenediaminetetraacetic acid

FITC:

fluorescein isothiocyanate

GPIb:

glycoprotein Ib

HEPES:

N-[2–hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid]

HUVEC:

human umbilical vein endothelial cells

IgG:

immunoglobulin

IU:

international unit

PBS:

phosphate-buffered saline

NEM:

N-ethyl-maleimide

PMSF:

phenyl–methyl–sulphonyl–fluoride

TSP-1:

thrombospondin-1

vWF:

von Willebrand factor

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  1. INSERM, U 553: IFR 105, Institut d’Hématologie, Université Paris VII Denis Diderot, Paris, France

    Noëlia Gomes, Chantal Legrand & Françoise Fauvel- Lafeve

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  1. Noëlia Gomes
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  2. Chantal Legrand
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  3. Françoise Fauvel- Lafeve
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Correspondence to Françoise Fauvel- Lafeve.

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Gomes, N., Legrand, C. & Lafeve, F.F. Shear Stress Induced Release of Von Willebrand Factor and Thrombospondin-1 in Uvec Extracellular Matrix Enhances Breast Tumour Cell Adhesion. Clin Exp Metastasis 22, 215–223 (2005). https://doi.org/10.1007/s10585-005-7359-5

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