Soluble Decoy Receptor 3 Induces Angiogenesis by Neutralization of TL1A, a Cytokine Belonging to Tumor Necrosis Factor Superfamily and Exhibiting Angiostatic Action
Journal
Cancer Research
Journal Volume
64
Journal Issue
3
Pages
1122-1129
Date Issued
2004
Author(s)
Abstract
TL1A is a member of the tumor necrosis factor superfamily and plays an important role in regulating endothelial cell apoptosis. A previous study shows TL1A is able to interact with death receptor 3 and decoy receptor 3 (DcR3). Here, we demonstrate that DcR3 is able to induce angiogenesis in human umbilical vein endothelial cells (HUVECs). DcR3 promotes HUVEC proliferation and migration and up-regulates matrix metalloproteinase-2 mRNA expression and enzyme activity. Furthermore, DcR3 enhances EC differentiation into cord vascular-like structures in vitro, as well as neovascularization in vivo. The effects of DcR3 on HUVECs are also mimicked by anti-TL1A and antideath receptor 3 antibodies. In contrast, human aortic endothelial cells, which do not express TL1A, are not responsive to DcR3 treatment, including cell proliferation, migration, and angiogenic differentiation. These data demonstrate DcR3 might not only help tumor cells to escape immune surveillance but also induce angiogenesis by blocking TL1A action in endothelial cells. The pathological role of DcR3 in promoting cancer progress raises the possibility to target DcR3 for antiangiogenic therapy in the future.
SDGs
Other Subjects
cytokine; death receptor 3; death receptor 3 antibody; decoy receptor 3; gelatinase A; messenger RNA; protein; soluble decoy receptor 3 protein; tl1a antibody; tl1a cytokine; tumor necrosis factor; unclassified drug; angiogenesis; animal cell; animal experiment; animal model; aorta; apoptosis; article; cancer growth; cell differentiation; cell migration; cell proliferation; chick embryo; controlled study; embryo; endothelium cell; enzyme activity; human; human cell; immunosurveillance; in vitro study; in vivo study; mouse; neovascularization (pathology); nonhuman; nucleotide sequence; priority journal; protein expression; protein interaction; reverse transcription polymerase chain reaction; tumor cell; umbilical vein; upregulation; Animals; Cell Division; Cell Movement; Cells, Cultured; Chickens; Endothelium, Vascular; HT29 Cells; Humans; Matrix Metalloproteinase 2; Membrane Glycoproteins; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Member 6b; RNA, Messenger; Tumor Necrosis Factor Ligand Superfamily Member 15; Tumor Necrosis Factor-alpha; Up-Regulation
Type
journal article