Effect of hypoxia on cellular adhesion to vitronectin and fibronectin

Cellular invasion of extracellular matrix (ECM) occurs during normal and pa thological settings. For cells to invade, they must adhere to the underlyin g substratum, break down barrier molecules, and detach from the substratum prior to migrating through the ECM. We previously demonstrated that incubat ion under reduced oxygen levels increases the in vitro invasiveness of trop hoblast and breast carcinoma cells, an effect linked to elevated expression of the cell surface receptor for urokinase-type plasminogen activator (uPA R). This study examined the role of oxygen, integrins and the urokinase-typ e plasminogen activator (uPA) system on the adhesion of trophoblast and bre ast carcinoma cells to the ECM molecules vitronectin and fibronectin. Compa red to exposure to 20 and 5% oxygen, exposure to 1% oxygen decreased adhesi on of these cells to vitronectin and fibronectin, an effect that was revers ible by re-exposure to 20% oxygen. Incubation in 1% oxygen also resulted in reduced expression of surface alpha (5) integrin. Furthermore, adhesion to vitronectin and fibronectin was reduced by compounds that interfere with i ntegrin function, such as EDTA, anti-integrin antibodies, or by antibodies that interfere with the binding of pro-uPA to uPAR, soluble uPAR, soluble v itronectin, phosphatidylinositol-specific phospholipase C, as well as plasm inogen activator inhibitor-1. These findings suggest an important role for oxygen in the regulation of cellular invasion, possibly in part through its effects on integrin and PAR-mediated mechanisms of adhesion. (C) 2001 Acad emic Press.