Inhibitor of DNA binding-4 promotes angiogenesis and growth of glioblastoma multiforme by elevating matrix GLA levels.
Inhibitor of differentiation-4 is highly expressed in glioblastoma multiforme (GBM). We report a novel pro-angiogenic function for inhibitor of differentiation-4 in the growth of glioblastoma xenografts. Tumor-derived cell cultures expressing elevated levels of ID4 produced enlarged xenografts in immunosuppressed mice that were better vascularized than corresponding control tumors and expressed elevated matrix GLA protein (MGP) that mediated enhanced tumor angiogenesis. Inhibition of MGP resulted in smaller and less vascularized xenografts. Our finding shows a novel function for ID4 in tumor angiogenesis, and identifies ID4 and MGP as possible therapeutic targets for GBM.
Kuzontkoski
P M
PM
Department of Pediatrics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA.
Mulligan-Kehoe
M J
MJ
Harris
B T
BT
Israel
M A
MA
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005909:Glioblastoma / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000502:physiology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D051796:Inhibitor of Differentiation Proteins; D000097568:Matrix Gla Protein; C490128:ID4 protein, human