Shear stress induced release of von Willebrand factor and thrombospondin-1 in HUVEC extracellular matrix enhances breast tumour cell adhesion.
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.
Gomes
Noëlia
N
INSERM, U 553: IFR 105, Institut d'Hématologie, Université Paris VII Denis Diderot, Paris, France.
Legrand
Chantal
C
Fauvel-Lafève
Françoise
F
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D013314:Stress, Mechanical; D019700:Thrombospondin 1 / Q000502:physiology*; D014841:von Willebrand Factor / Q000502:physiology*
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D019700:Thrombospondin 1; D014841:von Willebrand Factor