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IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
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IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
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IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma

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IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma
Journal Article

IGFBP2 promotes vasculogenic mimicry formation via regulating CD144 and MMP2 expression in glioma

2019
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Overview
Vasculogenic mimicry (VM) refers to the fluid-conducting channels formed by aggressive tumor cells rather than endothelial cells (EC) with elevated expression of genes associated with vascularization. VM has been considered as one of the reasons that glioblastoma becomes resistant to anti-VEGF therapy. However, the molecular basis underlying VM formation remains unclear. Here we report that the insulin-like growth factor–binding protein 2 (IGFBP2) acts as a potent factor to enhance VM formation in glioma. Evidence showed that elevated IGFBP2 expression was positively related with VM formation in patients with glioma. Enforced expression of IGFBP2 increased network formation of glioma cells in vitro by activating CD144 and MMP2 (Matrix Metalloproteinase 2). U251 cells with stable knockdown of IGFBP2 led to decreased VM formation and tumor progression in orthotopic mouse model. Mechanistically, IGFBP2 interacts with integrin α5 and β1 subunits and augments CD144 expression in a FAK/ERK pathway-dependent manner. Luciferase reporter and ChIP assay suggested that IGFBP2 activated the transcription factor SP1, which could bind to CD144 promoter. Thus, IGFBP2 acts as a stimulator of VM formation in glioma cells via enhancing CD144 and MMP2 expression.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject

13/44

/ 13/89

/ 13/95

/ 14/1

/ 14/19

/ 631/67/1922

/ 631/67/2328

/ 82/80

/ 96/35

/ Analysis

/ Animals

/ Apoptosis

/ Bevacizumab

/ Brain Neoplasms - blood supply

/ Brain Neoplasms - genetics

/ Brain Neoplasms - pathology

/ Care and treatment

/ Cell Biology

/ Cell Line, Tumor

/ Cell Movement - genetics

/ Development and progression

/ Endothelial cells

/ Endothelial growth factors

/ Endothelium

/ Gelatinase A

/ Gene expression

/ Gene Expression Regulation, Neoplastic

/ Genes

/ Genetic aspects

/ Genetic regulation

/ Glioblastoma

/ Glioblastomas

/ Glioma

/ Glioma - blood supply

/ Glioma - genetics

/ Glioma - pathology

/ Glioma cells

/ Gliomas

/ Human Genetics

/ Humans

/ Hyaluronan Receptors - genetics

/ Hyaluronan Receptors - metabolism

/ Insulin

/ Insulin-Like Growth Factor Binding Protein 2 - genetics

/ Insulin-Like Growth Factor Binding Protein 2 - physiology

/ Insulin-like growth factor I

/ Insulin-like growth factor-binding protein 2

/ Integrins

/ Internal Medicine

/ Luciferase

/ Male

/ Matrix metalloproteinase

/ Matrix Metalloproteinase 2 - genetics

/ Matrix Metalloproteinase 2 - metabolism

/ Medicine

/ Medicine & Public Health

/ Metabolic pathways

/ Metalloproteinase

/ Mice

/ Mice, Inbred BALB C

/ Mice, Nude

/ Mice, Transgenic

/ Mimicry

/ Mimicry (Biology)

/ Neovascularization, Pathologic - genetics

/ Neovascularization, Pathologic - pathology

/ Oncology

/ Protein binding

/ Signal Transduction - genetics

/ Sp1 protein

/ Tumor cells

/ Tumors

/ Vascular endothelial growth factor

/ Vascularization