Suspension state promotes extravasation of breast tumor cells by increasing integrin β1 expression

Abstract

Mechanical microenvironment can strongly affect the metastatic efficiency of circulating tumor cells. However, the effect of suspension state on their extravasation and the mechanisms involved are still unclear. To explore the influence of suspension state on extravasation (including adhesion, spreading and transendothelial migration) of breast tumor cells and its relevant molecular mechanism, MDA-MB-231 cells were cultured on poly (2-hydroxyethyl methacrylate) coated 6-well plates to minic the suspension state. Suspension state promoted adhesion, spreading and transendothelial migration of MDA-MB-231 cells to EAhy926 endothelial cells (ECs) monolayer under both the static condition and 0.5 dyne/cm2 flow shear stress (FSS). The number of cells adhered to ECs monolayer reached 2.15 (static condition, 3 d) and 1.67 (FSS, 3 d) times, and the number of migration reached 10.60 times, respectively, as compared to that in adhesion state. Moreover, MDA-MB-231 cells knockdown of integrin β1 provoked poor adhesion and transendothelial migration, as compared with MDA-MB-231 cells. But it made no difference in cell spreading. Our results implied the increasing expression of integrin β1 induced by suspension culture promoted the adhesion and transendothelial migration of MDA-MB-231 cells, but had no significant influence on their spreading.