Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo.
MAGE-D1 is a member of the MAGE family of proteins, and functions as an adaptor that mediates multiple signaling pathways. The current study for the first time provides evidence for a role of MAGE-D1 in the negative regulation of angiogenic activity in vitro and in vivo models. Our findings showed that MAGE-D1 over-expression significantly suppressed the angiogenic key events such as endothelial cell migration and invasion, adhesion on collagen I substrate, and in vitro differentiation into tube-like structures under both normoxic and hypoxic conditions. MAGE-D1 over-expression also inhibited in vivo angiogenesis in Matrigel plugs that were implanted subcutaneously in mice. With further experiments, we revealed that MAGE-D1 over-expression disrupted actin cytoskeleton organization and lamellipodia formation, and down-regulated HIF-1-dependent gene expression in endothelial cells under hypoxic conditions. These findings demonstrate a new function of MAGE-D1 in the regulation of angiogenesis and provide new insight into the ability of MAGE-D1 to suppress the growth and angiogenic response of endothelial cells by interfering with HIF-1-dependent gene expression, and actin cytoskeleton reorganization, suggesting that MAGE-D1 might be a novel inhibitor of angiogenesis in vitro and in vivo.
Shen
Wei-Gan
WG
Medical College of Yangzhou University, 16 Huai Hai Road, Yangzhou 225000, Jiangsu Province, PR China. weiganshen@yahoo.com.cn
Xue
Qing-Yu
QY
Zhu
Jun
J
Hu
Ben-Shun
BS
Zhang
Yu
Y
Wu
Yi-Ding
YD
Su
Qing
Q
D000199:Actins / Q000378:metabolism; D000256:Adenoviridae / Q000502:physiology*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000821:virology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics; D007797:Laminin / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism
D000199:Actins; D000951:Antigens, Neoplasm; D004338:Drug Combinations; D051793:Hypoxia-Inducible Factor 1; D007797:Laminin; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen