Clinical & Experimental Metastasis

, Volume 22, Issue 3, pp 215–223 | Cite as

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

  • Noëlia Gomes
  • Chantal Legrand
  • Françoise Fauvel- Lafeve
Article

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/cm213) 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.

Keywords

adhesion breast tumour cells endothelial cells extracellular matrix integrins platelets shear stress thrombospondin-1 von Willebrand factor 

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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Copyright information

© Springer 2005

Authors and Affiliations

  • Noëlia Gomes
    • 1
  • Chantal Legrand
    • 1
  • Françoise Fauvel- Lafeve
    • 1
  1. 1.INSERM, U 553: IFR 105, Institut d’HématologieUniversité Paris VII Denis DiderotParisFrance

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