CD44 Controls Endothelial Proliferation and Functions as Endogenous Inhibitor of Angiogenesis

CD44 transmembrane glycoprotein is involved in angiogenesis, but it is not clear whether CD44 functions as a pro- or antiangiogenic molecule. Here, we assess the role of CD44 in angiogenesis and endothelial proliferation by using Cd44-null mice and CD44 silencing in human endothelial cells. We demonstrate that angiogenesis is increased in Cd44-null mice compared to either wild-type or heterozygous animals. Silencing of CD44 expression in cultured endothelial cells results in their augmented proliferation and viability. The growth-suppressive effect of CD44 is mediated by its extracellular domain and is independent of its hyaluronan binding function. CD44-mediated effect on cell proliferation