Abstract
Dentin matrix protein 1 (DMP1) is a member of the Small Integrin‐Binding LIgand N‐linked Glycoproteins (SIBLINGs) family, a group of proteins initially described as mineralized extracellular matrices components and more recently implicated in several key steps of cancer progression, including angiogenesis. Although pro‐angiogenic activities have been demonstrated for two SIBLINGs, the role of DMP1 in angiogenesis has not been addressed yet. We found that DMP1 inhibited the proliferation while it stimulated migration and tubulogenesis of human umbilical vein endothelial cells (HUVEC), thus promoting differentiation of endothelial cells. Further investigation of DMP1 mechanism of action evidenced a CD44‐dependent G1‐block and an increased p27Kip1 and VE‐cadherin expression in HUVEC.Our data identify DMP1 as a new regulator of angiogenesis that turns on the switch of the endothelial cell phenotype from proliferative to differentiated, through a CD44‐dependent differentiation program that links up with a VE‐cadherin pathway mediating contact inhibition of endothelial cell growth.
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